We designed the present study to clarify whether the development of nephropathy was accelerated by a combination of hypertension and non-insulin-dependent diabetes. Spontaneously hypertensive rats with non-insulin-dependent diabetes induced by neonatal streptozotocin treatment (25.0-75.0 mg/kg) were separated into severely or mildly diabetic groups according to their non-fasting plasma glucose levels at 12 weeks of age and the findings were compared with the data on a control group treated with citrate buffer alone. The natural courses of urinary excretion rate of total protein, the molecular composition by sodium dodecyl sulfate polyacrylamide gel electrophoresis with laser densitometer and N-acetyl-beta-D-glucosaminidase were measured in the three groups from 12 weeks until 36 weeks of age. Total urinary protein in the control group decreased with age (p less than 0.05), while in the mildly diabetic group changes were nil; in the severely diabetic group, however, the excretion rates of total urinary protein and high molecular weight protein consistently and progressively increased with age (p less than 0.05). The low molecular weight protein continuously decreased with age in the mildly diabetic and control groups (p less than 0.05), while in the severely diabetic group there was no decrease after 28 weeks of age. The urinary N-acetyl-beta-D-glucosaminidase markedly increased (p less than 0.05) in the severely diabetic group throughout the period compared with findings in the control group, but drastically decreased (p less than 0.05) in the mildly diabetic group with age.(ABSTRACT TRUNCATED AT 250 WORDS)