Sera of 153 children with rheumatic diseases were assayed by an enzyme-linked immunosorbent assay (ELISA) for the presence of antibodies to native (n) and to denatured (d) type II collagen (IIC). Among the study population, antibodies to nIIC were detected in 47% with juvenile rheumatoid arthritis (JRA), 21% with spondyloarthropathies, 37% with other rheumatic diseases, 70% with adult onset rheumatoid arthritis (RA), and in less than 1% of nonrheumatic disease control groups. Antibodies to dIIC were detected in 42% of children with JRA, 41% with spondyloarthropathies, 37% of children with other rheumatic diseases, 67% with adult onset RA, and in less than 6% of nonrheumatic disease control groups. These results indicate that, when compared to nonrheumatic disease control groups, antibodies to both nIIC and dIIC occur significantly more frequently in children with a variety of rheumatic diseases.