Families with a two-generational history of affective disorder and well and ill sibs were selected from a population of bipolar manic-depressive patients and typed for HLA antigens, blood groups, serum proteins and red cell enzymes. Segregation of specific HLA alleles was not associated with affective illness across family pedigrees. Further, no significant associations were found between affective disorder and ABO, Rh, MNSs blood groups or Hp, EsD, C3, Gc or PGM. Using the lod score method of Morton (1955) for determining linkage, these data indicated that close linkage is unlikely for affective disorder and HLA alleles, haptoglobin, Rh factor, or ABO blood groups.