Rheumatoid factor (RF) was assayed in 354 unaffected first degree relatives from 59 families with multicase rheumatoid arthritis (RA), using both the latex test and ELISA for different RF isotypes. The association between HLA and presence of RF was also analyzed. In all, 39% of the relatives were positive for at least one class of RF compared to 7% positive for latex. There were no differences between the sexes in these rates. There were significant excess rates of HLA-DR4 in RF positive when compared to the RF negative relatives. The HLA-DR4 frequency in these RF positive RA negative individuals is similar to that observed in series of RA positive patients. Thus HLA status did not usefully discriminate between RA positive and RA negative but RF positive individuals in these families.