MYCIN was an early backward chaining expert system that used black box to identify bacteria causing severe infections, such as bacteremia and meningitis, and to recommend antibiotics, with the dosage adjusted for patient's body weight — the name derived from the antibiotics themselves, as many antibiotics have the suffix "-mycin". The Mycin system was also used for the diagnosis of blood clotting diseases. MYCIN was developed over five or six years in the early 1970s at Stanford University. It was written in Lisp as the doctoral dissertation of Edward Shortliffe under the direction of Bruce G. Buchanan, Stanley N. Cohen and others.

MYCIN emerged from the Stanford Heuristic Programming Project. MYCIN demonstrated the potential for expert systems in building high-performance medical reasoning programs. MYCIN is often viewed as a pioneer in the field of expert systems, even being referred to as the "grandaddy of them all-the one that launched the field" by Dr. Allen Newell.

MYCIN led to the EMYCIN expert system shell ("essential MYCIN") for acquiring knowledge, reasoning with it, and explaining the results, without the specific medical knowledge. It can be described as "EMYCIN = Prolog + uncertainty + caching + questions + explanations + contexts - variables". An introduction is in Chapter 16 of Paradigms of Artificial Intelligence Programming (PAIP).

MYCIN operated using a fairly simple inference engine and a knowledge base of ~600 rules by obtaining individual inferential facts identified by experts and encoding such facts as individual production rules. No other AI program at the time contained as much domain-specific knowledge clearly separated from its inference procedures as MYCIN. It would query the physician running the program via a long series of simple yes/no or textual questions. At the end, it provided a list of possible culprit bacteria ranked from high to low based on the probability of each diagnosis, its confidence in each diagnosis' probability, the reasoning behind each diagnosis (that is, MYCIN would also list the questions and rules which led it to rank a diagnosis a particular way), and its recommended course of drug treatment. MYCIN could additionally respond to queries by physicians related to why it asked the user a certain question, how it arrived at a conclusion, and why it did not consider certain factors.

The developers performed studies showing that MYCIN's performance was minimally affected by perturbations in the uncertainty metrics associated with individual rules, suggesting that the power in the system was related more to its knowledge representation and reasoning scheme than to the details of its numerical uncertainty model. Some observers felt that it should have been possible to use classical Bayesian statistics. MYCIN's developers argued that this would require either unrealistic assumptions of probabilistic independence, or require the experts to provide estimates for an unfeasibly large number of conditional probabilities.

Subsequent studies later showed that the certainty factor model could indeed be interpreted in a probabilistic sense, and highlighted problems with the implied assumptions of such a model. However the modular structure of the system would prove very successful, leading to the development of graphical models such as Bayesian networks.

A context in MYCIN determines what types of objects can be reasoned about. They are similar to variables in Prolog, or environment variables in operating systems.

In MYCIN it was possible that two or more rules might draw conclusions about a parameter with different weights of evidence. For example, one rule may conclude that the organism in question is E. Coli with a certainty of 0.8 whilst another concludes that it is E. Coli with a certainty of 0.5 or even −0.8. In the event the certainty is less than zero the evidence is actually against the hypothesis. In order to calculate the certainty factor MYCIN combined these weights using the formula below to yield a single certainty factor: