In a group of seventy-three diabetics, a statistically significant (P < 0.001) increase (+ 41 per cent) of serum N-acetyl-beta-glucosaminidase activity was found. The enzyme level seemed to correlate with both the vascular complications (either microangiopathic or macroangiopathic in nature) and the blood sugar level measured simultaneously. In fact, in patients with moderately elevated glycemia (145 mg./100 ml. ± 41) and without vasculopathies, the enzymatic activity was slightly changed (P > 0.05), while the activity was significantly (P < 0.001) increased (+ 31 per cent), in diabetics with essentially similar gly-cemia (151 mg./100 ml. ± 30) but with vasculopathies, and even more elevated (+ 80 per cent, P < 0.001) in diabetics without vasculopathies but with marked hyper-glycemia (309 mg./100 ml. ± 160). Since lysosomal enzymes, to which N-acetyl-beta-glucosaminidase belongs, are capable of degrading various compounds, these enzymatic changes were regarded as due to an activation of lysosomal enzymes in tissues, occurring in diabetes in response to the metabolic need of degrading either mucopolysaccharides and glycoproteins (as in diabetics with vasculopathies), or various constituents of cells themselves in a context of increased tissue catabolism (as in decompensated diabetics). However, the possibility cannot be excluded that the enzyme is elevated merely because of decreased lysosome stability. Reduction in the destruction rate of the enzyme might also contribute to its elevation.