We studied whether patients hospitalized for LSD psychosis are clinically separable from acute schizophrenics. The family histories, manifest symptoms, premorbid adjustment, and profiles on an extensive test battery were analyzed for 52 LSD psychotics and 29 matched first-break schizophrenics. The LSD patients did not differ from schizophrenics in incidence of psychosis or suicide among the parents. However, the rate of parental alcoholism for LSD psychotics far exceeded that for schizophrenics and the general population. The two groups were distinguished on some clinical features but were equivalent in premorbid adjustment, on most cognitive measures when initially hospitalized or reassessed three to five years later, and in number of subsequent rehospitalizations. Thus, in most respects the LSD psychotics were fundamentally similar to schizophrenics in geneaology, phenomenology, and course of illness. The findings supported a model of LSD psychosis as a drug-induced schizophreniform reaction in persons vulnerable to both substance abuse and psychosis.