There is ample evidence that cell-mediated immune mechanisms are crucial in the initiation of insulin-dependent diabetes mellitus (IDDM). Therefore, the role of cytokines in the pathogenesis of IDDM was investigated in 51 patients with IDDM, in comparison with 20 normal controls. The patients were divided into three groups, group 1 consisting of 31 newly diagnosed type 1 diabetics, in group 2 IDDM had been diagnosed for between 2 months and 2 years, and in group 3 onset had occurred 2-20 years before. Interleukin 1 (IL 1) activity was measured by the thymocyte co-stimulator assay, and interleukin 2 (IL 2) using IL 2 dependent cell lines. Peripheral blood monocyte IL 1 production was not altered under basal conditions. However, silica-stimulated IL 1 release was normal in patients with newly diagnosed or short-term disease, but was significantly decreased in long-term diabetics. Peripheral blood T-lymphocyte IL 2 production at onset of IDDM was normal under basal conditions, and upon optimal stimulation with concanavalin A (ConA) and phorbol myristate acetate (PMA). However, in the two groups with longer standing diabetes, basal and stimulated IL 2 release was decreased. We conclude that monocytes and T-lymphocytes from patients with diabetes mellitus have a diminished capacity to release IL 1 and IL 2 only later in the course of the disease. At the time of manifestation of disease, IL 1 and IL 2 production is normal in type-I diabetes mellitus.