Diabetic nephropathy with renal failure is a major cause of death among juvenile diabetics. It is as yet unknown why some diabetics suffer from this serious renal complication while others do not, in spite of long duration of diabetes. For therapeutic reasons it is of the utmost importance to find out which patients are at risk long before the manifestation of renal insufficiency. Juvenile diabetics are know to have an increased frequency of some HLA antigens. The relationships between the HLA-A, HLA-B and HLA-C antigens and diabetic end-stage nephropathy were therefore evaluated in the present study. The study comprised 121 insulin-dependent diabetics with renal failure (mean age at onset of diabetes 13.4 leads to 7.6 (SD) years, mean pre-uraemic duration of diabetes 21.7 leads to 4.7 years), and 36 insulin-dependent diabetics (mean age at onset of diabetes 16.5 leads to 8.4 years) without renal failure despite long mean duration of diabetes (32.5 leads to 5.1 years). We found the expected significant increase in B8 and B15 and a decrease in B7 frequencies in the diabetics compared with the non-diabetic population, but no difference was found between uraemic and non-uraemic diabetics. Neither the early onset of diabetes nor the rapid appearance of renal failure was associated with any HLA frequency. The data therefore do not provide evidence of the involvement of B8 or B15 allele-associated mechanisms in the disease process leading to diabetic nephropathy with renal failure. There was a significant difference (p corrected less than 0.01) between the frequency of Bw22 in uraemic diabetics (14%) and that in non-diabetics (5%) while the frequency was near normal in non-uraemic diabetics. Further data are needed to confirm the possible association of Bw22 with diabetic nephropathy.