The activity of collagenase and certain lysosomal hydrolases (cathepsin B1, cathepsin D, beta-glucuronidase and beta-N-acetyl glucosaminidase) was studied in serum and tissues of rats with streptozotocin- or alloxan-induced diabetes. The activity of serum lysosomal enzymes was increased in both groups (p less than 0.05). Both streptozotocin- and alloxan-diabetic animals showed significantly higher dermal collagenase activity than those of controls (p less than 0.01), but the liver and spleen showed similar activities; there was a significant decrease in the renal collagenase activity of streptozotocin-diabetic rats (p less than 0.05). Comparison of the alloxan- or streptozotocin-treated groups with control animals showed an increase in lysosomal enzymes (cathepsin B1, cathepsin D, beta-glucuronidase and beta-N-acetyl glucosaminidase in skin, liver and spleen) (p less than 0.05) but beta-N-acetyl glucosaminidase was unchanged in the spleen of streptozotocin-diabetic rats. There was no difference in renal cathepsin B1 and D in control versus alloxan-diabetic rats, but there was an increase in beta-glucuronidase and beta-N-acetyl glucosaminidase (p less than 0.05). The streptozotocin-diabetic animals showed decreased activities of renal lysosomal enzymes (p less than 0.05), but similar activity of cathepsin D to the control animals.