The possible association between residual B-cell function and specific HLA antigens in Type 1 (insulin-dependent) diabetes was studied in a cross-sectional series of 144 diabetic children and adolescents, as well as in a prospective series of 44 newly diagnosed diabetic subjects who were observed for the initial 2 years of their diabetes. In the cross-sectional study, the HLA-Dw3/Dw4 heterozygotes had a lower mean serum C-peptide concentration during 1980, 0.03 +/- 0.01 nmol/l (mean +/- SEM) vs. 0.09 +/- 0.01 nmol/l (p less than 0.02), as well as a lower 24-h urinary C-peptide excretion, 0.27 +/- 0.06 nmol/m2 vs. 1.34 +/- 0.19 nmol/m2 (p less than 0.05), than the other subjects. In addition, the Dw3/Dw4 heterozygotes had a clinical remission of shorter duration, 113 +/- 47 days vs. 203 +/- 22 days (p less than 0.05), and a higher mean glycosylated haemoglobin level during 1980, 14.8 +/- 0.05% vs. 13.7 +/- 0.2% (p less than 0.05), than those without the Dw3/Dw4 combination. In the prospective study the serum C-peptide concentrations were of the same magnitude in the Dw3/Dw4 heterozygotes and the other subjects during the first month. Subsequently the C-peptide concentrations in the subjects with the Dw3/Dw4 combination started to decrease 2 months earlier than in the other subjects. The Dw3/Dw4 children had a significantly lower serum C-peptide concentration at 21 months, 0.01 +/- 0.01 nmol/l vs. 0.13 +/- 0.02 nmol/l (p less than 0.01), and at 24 months, 0.03 +/- 0.01 nmol/l vs. 0.12 +/- 0.02 nmol/l (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)