We have identified by means of hystocompatibility typing that patients with the pheno-type HLA-Bw44 are at risk for development of autoantibodies such as antinuclear antibodies, the lupus anticoagulant and antineuronal antibodies, when exposed to prolonged therapy with chlorpromazine. The subgroup of patients with Bw44 and autoantibodies has higher tardive dyskinesia scores than the rest of the patients. Recently we have completed the typing on the same patient population of the four complement proteins, Bf, C2, C4A and C4B (complotypes), which are also encoded as the HLA genes in the short arm of Chromosome 6. We have made a preliminary analysis of the phenotypes of the 27 patients and assigned the hypothetical haplotypes by deduction. In 11 of 24 patients with autoantibodies and the HLA antigen Bw44, it was found that Bw44 segregated with the antigen DR7 and the complotype FC31. The HLA Bw44 was found to be inherited along with DR7 and FC31 in 13 of 350 normal controls and it constitutes one of eight extended haplotypes identified in man. The group of patients with CPZ-induced autoantibodies and the extended haplotype HLA-Bw44-DR7-FC31 had eight of the nine highest tardive dyskinesia scores. HLA-A,B,C and DR alleles will be detected by alloantisera from immunized humans using the microlymphotoxicity assay. The complotypes BF, C2, CA4, C4B are detected by two-dimensional immunoelectrophoresis and immunofixation with specific antisera. In the present study we propose to perform genotyping of family members of individuals with the projected haplotype Bw44-DR7-FC31. This will permit us to ascertain that the complotype is inherited with Bw44 and DR7. If the presence of Bw44-DR7, FC31, is confirmed by these family studies, it would suggest that the extended haplotype Bw44-DR7-FC31 is a marker for autoimmunity and possibly for development of severe tardive dyskinesia.