We studied autologous mixed leukocyte reaction (AMLR) in type 1 (insulin-dependent) diabetes mellitus (IDDM) patients, their healthy siblings and healthy schoolchildren, Blood samples from the patients were drawn within 1 week after hospitalization and 2 months later. AMLR was significantly depressed in the patients when compared to healthy siblings or other healthy controls. In addition, the mean AMLR responsiveness of the healthy control group exceeded that of healthy siblings. The production of IL-2 in AMLR was impaired in the patient group and the defective AMLR could be restored by addition of exogenous IL-2 in 7-10 patient cultures. However, in 3-10 patients addition of IL-2 induced no enhancement of proliferation. While the patients in general had raised levels of activated T lymphocytes these three patients had higher numbers of activated T cells than other patients. Defective AMLR and presence of activated T cells may be related and may play a role in the pathogenesis of IDDM.