Monoclonal antibodies were used to characterize peripheral T-lymphocyte subpopulations in 23 patients with type I diabetes mellitus. Initial measurements were made at diagnosis and in 10 of the patients further studies were carried out at 1, 3 and 6 months. T-cell subsets were also measured in 16 patients with type II diabetes, in 16 patients with various autoimmune diseases and in 17 healthy control subjects. At diagnosis, the type I diabetic patients showed a significant decrease in the percentage of cytotoxic/suppressor cells. Both total T-cells and helper/inducer cells were normal. However, when the helper/inducer population was analyzed in the context of islet cell antibodies (ICAs), it was found that those patients possessing ICAs had significantly higher proportions of helper/inducer cells than those lacking them. A significant inverse correlation was seen between the proportions of total T-cells and NK/K cells. At I month, the proportions of cytotoxic/suppressor cells returned to normal, whilst the helper/inducer cells showed a transient depression. By 6 months, the only change seen was a significant increase in the percentage total t-cells. No relationship was found between T-cell subset perturbation and metabolic control, as assessed by measurement of hemoglobin AI (HbAI). The type II diabetic patients showed a significant increase in the percentage of total T cells. The autoimmune patients also showed a significant increase in the proportions of total T-cells; this appeared to reflect an increase in the helper/inducer subset. In the autoimmune patients these findings occurred in conjunction with significant decreases in the absolute numbers of each T-cell subset. It is surmised that, in some cases of type I diabetes, alterations in immune homeostasis may permit autoimmune processes, which lead to cell damage at the onset of diabetes.