Two three-generation families from Northern Sweden with rheumatoid arthritis (RA) were clinically examined. Tissue typing was performed for HLA-A, -B, -C, and -DR antigens. No disease-associated haplotype could be defined within these families. Six of nine members with RA were HLA-DR4 positive. Both families had a HLA-DR4 containing haplotype in the first generation and second-generation members married DR4 positive individuals, which probably increased the risk to develop RA in the third-generation members.