Previously we have proposed that a locus for schizophrenia could be present on the sex chromosomes based on observations of increased numbers of same sex siblings with schizophrenia and an excess of sex chromosome aneuploidies among cohorts of schizophrenics. Since male to male transmission occurs in schizophrenia, homologous loci on the X and Y chromosomes were postulated. In previous studies small positive lod scores were obtained for loci from Xp11.4 to Xq12, reaching a maximum of 2.10 at 0.0% recombination at MAOB, assuming X-linked recessive inheritance in these families (DeLisi LE. et al. 1994). We are examining the possibility of X-Y linkage in schizophrenia by analysing X chromosome typing results with an X-linked model, an X-Y linkage model and selecting families for evidence of maternal inheritance and absence of male to male transmission of psychosis. Under these conditions the lod score for linkage to the locus DXS7 reached a maximum of 1.5 at 10% recombination, assuming X-linked recessive inheritance in these families (n=44). Further investigations focusing on this region in expanded and independent groups of new families in collaborating studies are in progress.