Some 40 years ago phencyclidine (PCP) was developed as the prototype of a proposed new class of ‘dissociative’ general anesthetics, so called because it induced a marked dissociation from the environment without complete loss of consciousness. In the earliest clinical trials of PCP anesthesia, it was observed that as many as half the subjects experienced severe psychotic reactions during and beyond emergence. This striking clinical observation at once marked the failure of PCP as a suitable general anesthetic, and the beginning of a remarkable new era in basic and clinical neuroscience which can serve as an example of the interaction between clinical observation and basic science. At once, clinical researchers turned their focus upon the characterization of the PCP-induced psychosis, and recognized striking similarities between PCP-induced symptoms and signs and both the negative and positive symptoms of schizophrenia, proposing the PCP psychosis as a new model of that illness. Several years later PCP suddenly emerged as a major drug of abuse, with the result that emergency rooms and psychiatric inpatient units were observing and treating large numbers of these patients, in many of whom a diagnosis of schizophrenia could not be ruled out until toxicological analyses were performed. This natural experiment yielded a huge amount of additional data, and contributed a strong public-health based impetus to research into the nature and treatment of PCP intoxication.