In a group of 90 diabetics, an increased serum activity (+137 per cent, p<0.001) of the lysosomal enzyme acid phosphatase was found. The increase was moderate (+55 per cent, p<0.01) in uncomplicated diabetics with slightly elevated glycemia (148 ± 24 mg glucose/100 ml), while it was more accentuated (about twice normal, p<0.001) in diabetics with either vasculopathies (micro- or macroangiopathy) or marked hyperglycemia (343 ± 108 mg glucose/100 ml). Serum aspartate and alanine aminotransferases were normal. Thus, acid phosphatase in diabetes behaves similarly to other lysosomal enzymes: beta-glucuronidase and N-acetyl-beta-glucosaminidase. This is a further evidence of lysosomal enzyme activation in diabetes, apparently linked to both the degree of metabolic decompensation and the presence of vasculopathies. Since acid phosphatase, unlike beta-glucuronidase and N-acetyl-beta-glucosaminidase, is not concerned with degradation of mucopolysaccharides and glycoproteins, the higher activity found in vasculopathic diabetics would indicate that in these patients the activation process is not restricted to the enzymes capable of degrading the aforementioned compounds, which accumulate in the walls of diseased vessels, but involves a variety of lysosomal hydrolases.