Lack of Fyn tyrosine kinase increases alcohol sensitivity. Fyn phosphorylates a component of the NMDA receptor, which may be involved in schizophrenia. The Fyn gene is located on human chromosome 6q21, to which linkage of schizophrenia has been suggested. We hypothesized that the Fyn gene is a candidate for predisposition to alcoholism and schizophrenia, and we performed a mutation study of the 5'-flanking region, all coding exons, and exon-intron junctions of the Fyn gene. The SSCP mutation analysis was performed in 48 unrelated alcoholics and 16 unrelated schizophrenics. Three polymorphisms, -93A/G in the 5'-flanking region, IVS10+37T/C in intron 10, and Ex12+894T/G in the 3'-untranslated region, were identified. A rare variant of Ex12+1162TG in the 3'-untranslated region was also detected. Neither missense nor nonsense mutations were found. Case-control studies using a larger sample of unrelated patients and controls did not reveal significant associations between these polymorphisms and alcoholism or schizophrenia. In addition, genotyping a microsatellite marker, D6S302, located in intron 10 of the Fyn gene, did not show a significant association between the marker and alcoholism or schizophrenia. Results of the present study did not provide evidence for the involvement of the genomic Fyn gene mutations in alcoholism or schizophrenia. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:716-720, 2000.