HLA-A, B, C, DR and DQ typing was performed in 381 Italian insulin-dependent diabetic patients and in 905 normal Italian subjects. The diabetic patients had significantly higher frequencies of HLA-Cw7, B8, B18, DR3, DR4, DQw2 and DQw3 and significantly lower frequencies of HLA-B17, Bw51, DR2, DR7 and DRw11. The frequency of heterozygosity for HLA-DR3/DR4 was significantly higher in patients who developed the disease in the first 2 years of life and DR3+/DR4-, DQw2 and DQw3 alleles were higher in those aged less than 14 years at onset. The HLA-DR4 allele was associated with onset of diabetes in autumn and HLA-B18 with onset in Autumn-winter. Diabetic children who were breast fed had a later onset of insulin-dependent diabetes mellitus than those who were bottle fed but these differences were independent of HLA typing (11.8 +/- 0.72 years vs 9.23 +/- 0.42 years; mean +/- SEM). We conclude that: (1) in general, HLA distribution in Italian insulin-dependent diabetic patients reflects previous data reported in other European and North American populations; (2) HLA-DR3 and DR4 are strongly associated with insulin-dependent diabetes in Italy as well, and these alleles seem to predispose to an earlier onset of the disease; and (3) breast feeding may delay the onset of the disease.