The nephrotic syndrome (NS) reported from Southern Africa is distinguished by unusual characteristics in African children and typical features among Indian children. A genetic basis for these differences is explored in 44 African and 33 Indian children with NS in this paper. HLA associations were detected in the 20 Indian children with minimal change NS (MCNS) and 12 African children with membranous NS. Previous studies of HLA antigens, which have all been performed on Caucasian children with MCNS or steroid-responsive NS (SRNS), have detected associations with HLAB and DR locus genes. In this report HLA Bw44, which is part of HLA B12, was found to be significantly more frequent in Indian children with MCNS or SRNS than in controls (45 and 12%, respectively, p less than 0.04; relative risk 5.8). In contrast, African children with membranous nephropathy had a significantly increased frequency of HLA Bw21 (15% in patients and 1% in controls, p less than 0.04; relative risk 22.1). HBsAg was positive in 9 of 11 patients tested in the latter group. We conclude that the interaction between heredity and environmental factors is central to the pathogenesis of membranous nephropathy and similar considerations may be important in the development of MCNS.