The sex chromosomes are strong candidates for a genetic locus for schizophrenia and the affective psychoses. Gender differences in the clinical expression of illness and familial risks, concordance for gender and illness in relatives, and an association of X chromosome anomalies with psychosis suggest an X chromosome locus. The presence of male-to-male transmission in some families, in the face of a lack of strong evidence for heterogeneity, specifically focuses the search within the pseudoautosomal region of the X and Y chromosomes where sequence homology and recombination takes place.