Normal polymorphonuclear leukocytes (PMNL) in contrast to diabetic PMNL, generated significant amounts of .NO and NO2 when challenged with opsonised zymosan. Diabetic neutrophils, on the other hand, responded either weakly or insignificantly to the same stimulants. However, in resting state the levels of .NO and NO2 were higher in diabetic as compared to normal PMNL. Diabetic serum factor (DSF) provoked a significant generation of .NO and NO2 in normal PMNL, a phenomenon found parallel to the enhancement in cytosolic cathepsin D activity in normal cells on insult with DSF.