OBJECTIVE: This paper is intended to help American clinicians and investigators further their understanding of the clinical use of clozapine by reviewing experience with the drug in Russia, where it was introduced 17 years before it became available in the United States. METHODS: Key articles on clozapine from the Russian clinical research literature were reviewed by the first two authors, former Russian clinical investigators. The third author comments briefly about the implications of this work from a contemporary American perspective. FINDINGS AND CONCLUSIONS: The review found that although clozapine was not widely distributed in Russia, it was investigated at several large psychiatric research institutions and hospitals. It was not reserved for neuroleptic-resistant disorders but instead was used with some success as a first-line treatment in acute disorders. Although no controlled clinical trials were conducted, results of long-term outcome studies of treatment-resistant schizophrenia were largely in agreement with those of controlled trials and clinical follow-up studies in the U.S. The studies found short-term gains for previously refractory patients as well as improvements in social functioning that continued for extended periods in some cases. Russian investigators described clozapine as an effective antipsychotic agent that lacked the extrapyramidal side effects of other neuroleptics.