We examined the blastogenic responses of lymphocytes to Staphylococcus aureus antigen in 49 uninfected non-insulin-dependent diabetic subjects and in 56 uninfected nondiabetic subjects. We found a significantly decreased response to this antigen in the diabetic patients (P less than 0.05). Diabetics whose blood sugar levels were less than 150 mg/dl showed significantly decreased responses, as did diabetics whose blood sugar levels were greater than 200 mg/dl. The use of fetal calf serum in place of autologous plasma did not correct the defect. In a smaller number of patients, we observed a decreased response to tetanus toxoid, which was significant (P less than 0.05). The response to phytohemagglutinin was not significantly different from normal controls (P greater than 0.4). These results indicated that non-insulin-dependent diabetics, as well as insulin-dependent diabetics (previously reported), show decreased responses to S. aureus antigen and to tetanus toxoid. This defect apparently is not related to blood glucose levels or other serum factors.