In this long-term prospective study, including 45 diabetic children and adolescents under the age of 20 years, insulin antibodies and other immunological factors (circulating immune complexes, autoantibodies, etc.) were compared before and during a two-year follow-up after a switch-over from monocomponent porcine insulins to monocomponent semisynthetic human insulins. IgG insulin antibodies were detected in 21 children out of 45 (47%) at a mean level of 0.96 mU/ml (0.77-1.15). A significant and important decrease of both the number of patients having insulin antibodies and the level of insulin antibodies was observed 18 months after the switch-over. After 24 months, IgG insulin antibodies were only present in 5 patients (11%) at a mean level reduced by half (0.53 mU/ml; p less than 0.05). Four patients out of the five (80%) had HLA-DR3 DR4 antigens while this phenotype was only prevalent in 26% of the initial patient cohort. On the other hand, 3 months after the transfer, there was a significant and persistent decrease (by half) of non-specific immune complexes (39% of the patients with porcine insulins) which did not appear to correlate with the level of insulin antibodies. The prevalence of autoantibodies and of antinuclear factors showed no significant variations. The practical implication of these findings is that the use of semisynthetic human insulins could be of interest in patients previously treated by porcine insulins.