Peripheral blood lymphocytes transformed significantly to denatured type I collagen in 22 of 38 patients with rheumatoid arthritis (58%), 1 of 9 patients with Reiter's disease (P less than 0.05), and 9 of 32 controls (28%) (P less than 0.01). Determination of HLA antigens revealed significant differences between 24 rheumatoid arthritis (RA) patients and a control population for HLA-DRw4 (75% versus 23%). No correlation was observed between lymphocyte transformation to collagen and antibodies to collagen, rheumatoid factor, stage or duration of RA, or HLA antigens.