The restriction fragment length polymorphisms (RFLPs) associated with neuropeptide Y (NPY) and somatostatin loci were used to assess the possibility of linkage to a locus for affective disorder (AD). When somatostatin haplotypes were assigned to members of 2 AD pedigrees under either rare dominant or recessive transmission, the LOD scores obtained at 0% recombination were inconsistent with linkage. Similar results were obtained with NPY under rare dominant inheritance. Comparison of the frequency of the genotypes deduced from the polymorphic alleles of gastrin-releasing peptide, NPY, somatostatin and substance P in normals vs patients with either AD or schizophrenia suggests the absence of association. The difference in the frequency of the 3.3 kb adenosine deaminase fragment in normals vs bipolar and schizophrenic patients is of borderline significance.