Patients with Sjögren's syndrome alone (Ss), Sjögren's syndrome with rheumatoid arthritis (Ss-RA), and Sjögren's syndrome with Raynaud's phenomenon (Ss-RP) were typed for the HLA DR and MT antigens. Ss-RA patients had higher frequencies of HLA DR4 than did Ss patients. HLA-DR4 was also increased in frequency in patients with Ss-RP. This group of patients also showed increases in frequencies of HLA DR3. MT2 frequencies were elevated in all 3 patient groups, while MT1 was only increased in Ss. Three families with multiple individuals with Sjogren's syndrome were typed for HLA antigens. The affected individuals inherited unique combinations of haplotypes, suggesting the possibility of haplotype interaction in predisposition to disease.