Significant HLA-DR and MT associations were observed with certain clinical and serologic manifestations of pauciarticular onset juvenile rheumatoid arthritis (PO-JRA). An increase in the MTI frequency was found in 56 children with PO-JRA in comparison to 95 normal controls. This association was limited to children with a younger age of onset (less than 6 years) and a persistent pauciarticular course. An increase in HLA-DRW8 and a decrease in DR4 were associated with a younger age of onset and antinuclear antibody (ANA) seropositivity. In addition, an increased frequency of DR5 was seen in ANA positive children. All of these HLA-DR and MT associations were independent of coassociating Ia specificities.