1. We have investigated the frequencies of the major histocompatibility complex class II alleles by restriction fragment length polymorphism analysis, using DR, DQ and DP complementary DNA probes, in 40 Caucasoid steroid-sensitive nephrotic children. 2. A significant association with HLA-DR7 was demonstrated (P = 2 x 10(-5); aetiological fraction 0.6). The DQB1 gene of HLA-DQw2 was present in 83% of our patients (P = 2 x 10(-4); aetiological fraction 0.7). We present evidence that it contributes a second susceptibility allele. 3. A weak association between the uncommon HLA-DP-Cp63 allele and the disease was also observed. 4. Our data suggest that the immune events in steroid-sensitive nephrotic syndrome are defined by a particular immunogenetic background involving the beta-chain genes of HLA-DR7 and HLA-DQw2.