Immunoblot positive sera from children with juvenile rheumatoid arthritis detected from 1 to greater than or equal to 10 proteins in HeLa nuclear sonicates. Thirty percent of the sera reacted with histone H1. Antibodies to at least 1 of 6 most frequently detected nonhistone proteins were present in 85% of the sera. Using immunopurified antibodies to each of the 6 common antigens, we found that 4 of them were associated with mitotic chromosomes. Most sera detected at least 1 of these 4 nonhistone chromosomal proteins. Fifteen percent of the sera immunoprecipitated ribonucleoproteins; some exhibited a novel specificity, precipitating mature transcripts of RNA polymerase III. When present, antibodies to a 45 kDa protein occur only in sera from children without iritis and not in those with active iritis. Overall, the antibody profiles were highly individual and did not appear to correlate with disease subtype or activity.