We studied HLA antigens in 105 unrelated American Caucasian patients with rheumatoid arthritis (RA), 70 of them with familial disease. HLA-DR4 was observed in 71% of familial RA, 63% of non-familial RA, and 27% of normal controls, confirming the already well-established association between HLA-DR4 and both familial and non-familial RA. HLA-B27 was present in 14.3% of patients, versus 8% of normal controls (p = 0.04), and was not more common in familial (10 of 70, or 14.3%) versus non-familial (5 of 35, or 14.3%) disease. These results are compared with those observed in Scandinavian patients.