Studies of the segregation of major psychiatric disorders in families are consistent with multiple threshold polygenic models rather than with major locus transmission. This does not however rule out the possibility of identifying major locus traits that correlate with disease susceptibility. One approach has been to ascertain the degree of association between well characterized genetic markers and psychiatric disorders. The theory and methodology of such association and linkage studies are reviewed. The results of such studies lead to the conclusion that the association of ABO and HLA subtypes with affective disorders and schizophrenia is extremely variable, although there may be an association between HLA A9 and paranoid schizophrenia. The alternative strategy has been to identify specific genetically transmitted traits which are associated with disorders, and so could represent potential etiological factors. A review of these studies points to the potential usefulness of cholinergic and GABA markers for susceptibility to affective disorders. CT scan traits and attentional variables appear to be the most promising indicators of susceptibility to schizophrenia. cDNA probes in restriction enzyme digests for regularly spaced polymorphisms, and restriction fragment length polymorphisms offer the promise of a radical expansion in the number of markers available for linkage studies.