In a study of HLA-DR phenotypes in patients with rheumatoid arthritis (RA) and controls from the Saskatoon area and in Newfoundland, we found that certain phenotypes occurred more frequently in the patients than in healthy controls in both populations ("increased risk phenotypes"). The reverse was also true: certain phenotypes were reduced or excluded from patients with RA compared with controls. Three increased risk phenotypes with twice the expected frequencies or more were HLA-DR1,DR4; DR4 and DR4,DR5. Four "protective" phenotypes with half or less the expected frequencies were HLA-DR1, DR5; DR2; DR2,DR3 and DR3,DR7. We speculate that at least for the DR3,DR7 phenotype, the protective effect may be due to a hybrid DQw2 molecule.