We have performed linkage analysis in 186 multiplex families to search for genes that predispose to schizophrenia. Under a model with partially dominant inheritance, moderately broad disease definition and assuming locus homogeneity, a lod score of 3.2 was obtained for D6S260 on chromosome 6p23. A multipoint lod score of 3.9 (P = 2.3 x 10(-5)) was achieved when the F13A1 and D6S260 loci were analysed, allowing for locus heterogeneity. Adjusted for testing of multiple models, the multipoint lod score of 3.9 under heterogeneity has a genome wide significance of between 5-8%. The nonparametric affected pedigree member test provided results (P = 3 x 10(-4)) also supporting this finding. Our findings provide supportive evidence for a susceptibility locus for schizophrenia on distal chromosome 6p, and support a model of locus heterogeneity.