Lymphocytes from kindreds containing five sibling pairs affected with regional enteritis were typed to ascertain the association between histocompatibility leukocyte antigens (HLA)-A and -B and regional enteritis. Also, the frequency of HLA antigens in 22 patients with nonfamilial cases of regional enteritis was compared to the frequency in 402 normal blood donors. No HLA haplotype was found in more than one kindred, and no HLA antigen was more prevalent in nonfamilial cases of regional enteritis than in the normal population. In the five affected sibling pairs, four shared both haplotypes (HLA identical), and one shared one haplotype. Only one unaffected sibling shared two haplotypes with an affected proband. The high frequency of HLA identity in affected siblings and the low frequency of identity in unaffected siblings suggest linkage between the histocompatibility locus and the development of regional enteritis. There appears to be a genetic component in kindreds with regional enteritis.