To determine whether patients with rheumatoid factor (RF)-negative, antinuclear antibody (ANA)-positive oligo/polyarthritis are clinically and immunogenetically distinct from RF-positive rheumatoid arthritis (RA) and whether this subset of patients is the adult counterpart of early-onset pauciarticular juvenile chronic arthritis (EOPA JCA), we retrospectively studied 20 adult patients with RF-negative, ANA-positive arthritis. After a median duration of 3.25 years, only half of our patients had active synovitis. Seventy-five per cent were completely or reasonably self-sufficient according to the HAQ index. In contrast to the results in a group of 30 RF-positive RA patients, the percentage of patients having at least one of the susceptibility alleles (HLA DR1 or HLA-DR4) was not significantly higher in patients with RF-negative, ANA-positive arthritis than in controls. Furthermore, none of our RF-negative, ANA-positive patients had two susceptibility alleles, whereas 16.5% of RF-positive RA patients had both DR1 and DR4 or DR4 homozygosity. In conclusion, our results show that patients with RF-negative, ANA-positive oligo/polyarthritis are immunogenetically distinct from RF-positive RA and tend to have a better articular prognosis. The absence of typical ocular features and of the characteristic HLA-DR markers suggests that these patients cannot be considered as the adult counterpart of EOPA JCA.