It is well known that infections in patients with diabetes mellitus are more severe, although there is controversy for increased susceptibility to them. Non-specific immune response mechanisms could be related to defense and/or susceptibility to pathogens. The aim of this study was to investigate the activity of several enzymes involved in the primary host defense mechanisms in non-insulin dependent diabetes mellitus (NIDDM). Twenty NIDDM females with a mean HbA(1c) level of 8.19% were included. No patient had clinical evidence of infection. As controls 20 healthy females were studied. The enzymes tested were dipeptidyl-peptidase I (DPP-I), cathepsin B and D, NADPH oxidase and superoxide dismutase (oxidative burst) and collagenase. Isolated leukocytes were incubated with the specific substrates in pyrogen free conditions. The intracellular enzyme activity was analyzed by flow cytometry. Collagenase enzymatic activity was similar in the three leukocyte subpopulations studied. Oxidative burst induction in monocytes was comparable between both groups. Enzyme activity of cathepsin B and D in all cell subsets, oxidative burst in PMN cells, and DPP-I in lymphocytes and monocytes from patients, was higher than those from healthy females (P<0.05). Overall, our findings demonstrate an enhanced functional status of several intracellular leukocyte enzymes in NIDDM. Furthermore, the increased oxidative burst induction and the consequent production of free radicals, may contribute to vascular complications. Other mechanisms - either from the non-specific or specific immune response - deserve investigation to establish if diabetic patients are more susceptible to infectious diseases.