Interleukin-1 (IL-1) has been implicated in the pathogenesis of rheumatoid arthritis (RA). IL-1alpha gene polymorphism was analysed for the exon V and promoter region in 51 patients with destructive and 47 with non-destructive RA, as well as in 94 controls. The two biallelic polymorphisms in the promoter region and the exon V were 100% linked. The rare IL-1A2 allele carriage rate was 45% in the control population. It was increased in destructive (54.4%) and decreased in non-destructive RA (26.8%, destructive versus non-destructive, p < 0.007). All indices of disease activity and joint destruction were significantly lower in the patients positive for IL-1A1, and higher in those positive for IL-1A2. The present findings suggest that this IL-1alpha gene polymorphism may contribute to the pathogenesis of chronic polyarthritis. The presence of the IL-1A2 allele could constitute a risk factor for the development of destructive arthritis and could be used early in the course of the disease as a prognostic marker.