There have been allegations of doping in the Tour de France since the race began in 1903. Early Tour riders consumed alcohol and used ether, among other substances, as a means of dulling the pain of competing in endurance cycling. Riders began using substances as a means of increasing performance rather than dulling the senses, and organizing bodies such as the Tour and the International Cycling Union (UCI), as well as government bodies, enacted policies to combat the practice.

Use of performance-enhancing drugs in cycling predates the Tour de France. Cycling, having been from the start a sport of extremes, whether of speed by being paced by tandems, motorcycles and even cars, or of distance, the suffering involved encouraged the means to alleviate it. Not until after World War II were sporting or even particularly health issues raised. Those came shortly before the death of Tom Simpson in the Tour de France of 1967. Max Novich referred to the Tour de France in a 1973 issue of New York State Journal of Medicine as "a cycling nightmare". Journalist Hans Halter wrote in 1998 that "For as long as the Tour has existed, since 1903, its participants have been doping themselves. For 60 years doping was allowed. For the past 30 years it has been officially prohibited. Yet the fact remains; great cyclists have been doping themselves, then and now."

Drug-taking in cycling predates the Tour de France. "It existed, it has always existed", said the French reporter and author, Pierre Chany, who followed 49 Tours before his death in 1996. The exhaustion of six-day races on the track was countered by the riders' soigneurs (the French word for "carer"), helpers akin to seconds in boxing. Among the treatments they supplied was nitroglycerine, a drug used to stimulate the heart after cardiac attacks and which was credited with improving riders' breathing. Riders suffered hallucinations from the exhaustion and perhaps the drugs. The American champion Major Taylor refused to continue the New York race, saying: "I cannot go on with safety, for there is a man chasing me around the ring with a knife in his hand."

Also used was strychnine, which in small doses tightened tired muscles. A track rider of the era said he had developed such a tolerance to the drug that he took doses large enough to kill smaller men. The use of strychnine, far from being banned, was thought necessary to survive demanding races, says the sports historian Alain Lunzenfichter.

The American specialist in doping, Max M. Novich, wrote: "Trainers of the old school who supplied treatments which had cocaine as their base declared with assurance that a rider tired by a six-day race would get his second breath after absorbing these mixtures." John Hoberman, a professor at the University of Texas in Austin, Texas, said six-day races were "de facto experiments investigating the physiology of stress as well as the substances that might alleviate exhaustion."

The first backers of races on the road were newspapers. Although Le Vélocipède Illustré, which was behind the world's first long-distance road race in November 1869, said its purpose was "to further the good cause of the bicycle" because "it must be determined that the bicycle can be raced over considerable distances with incomparably less fatigue than running", backing the race would also boost the newspaper's sales. In an era before radio and television, newspapers could build the drama of a race for weeks, rely on customers buying a further copy on the day to prepare for the riders to pass and then another next day to see what had become of them. Few people had travelled 130 km, at least not often, and the idea of doing it by bicycle and at as high a speed as possible when the roads were potholed and bicycles had wooden wheels and metal tyres was exciting. The result was that newspapers outdid each other in promotions. In 1891 came a race from Bordeaux to Paris. In the same year, Le Petit Journal went twice as far by running Paris–Brest–Paris over 1,200 km.

During a meeting at L'Auto in Paris, journalist Géo Lefèvre suggested a race right round France, not just one day but six, "like the six-day races on the track." The idea of bringing the excess of the indoors to the roads of the outdoors was born. And with it came the practices which had seen riders through their suffering.

The strongest drug in the early Tour de France was strychnine. Other than that, riders would take anything to survive the tedium, the pain and the exhaustion of stages that could last more than 300 km. That included alcohol, which was already strong in French culture and sometimes purer than water after World War I destroyed water pipes and polluted water tables, and ether. There are photographs of riders holding ether-soaked handkerchiefs to their mouths, or leaving them knotted under the chin so the fumes would deaden the pain in their legs. The smell, enough to turn a man's stomach said Pierre Chany, discouraged some but also showed the extent of suffering by others. Roger Lapébie, winner of the Tour in 1937, said he smelled ether "in the bunch near the finish; it used to be taken in a little bottle called a topette." Its use lasted decades; riders were caught using it as late as 1963.