Clinical and biological profiles at the onset of the disease, obtained retrospectively, and human leucocyte antigen typing were studied in 47 rheumatoid arthritis (RA) patients with severe articular damage (group 1) and in 47 patients with limited radiological abnormalities (group 2). The two groups were matched according to disease duration (mean: 8.1 yr). Systemic manifestations were more frequent in group 1. Erythrocyte sedimentation rate (ESR), platelet counts, C-reactive protein (CRP), rheumatoid factor and IgG titres were higher and haemoglobin level lower in group 1. HLA class II genotyping demonstrated that 95.7% of patients in group 1 were Dw4, Dw14 or DR1 as compared to 55.3% in group 2 and 37.1% in normal controls. Two RA-linked DRB1 genes were detected in 34.1% of patients in group 1, vs 8.5% in group 2 and 7.9% in controls. Multiple logistic regression analysis demonstrated that ESR, CRP and genetic markers were the most relevant independent variables and when combined could indicate the outcome in early RA. These data confirmed that different RA subtypes with different prognoses could be associated with particular clinical, biological and genetic profiles. Moreover, some of these factors could serve as predictive markers for outcome at the onset of RA.