Epidermal growth factor (EGF) concentrations in the plasma, kidneys and urine of 31 streptozotocin-diabetic rats and 21 insulin-treated diabetic rats were measured to study the role of EGF in initiating renal hypertrophy in the diabetic rats. Renal hypertrophy occurred from day 7 in the diabetic rats, but not in the insulin-treated rats. Renal EGF was not different between the diabetic and control rats, while that in the insulin-treated rats was significantly less than in the diabetic rats. There were no significant changes in plasma EGF in any of the rats. Urine EGF was 119 +/- 7.9 ng/day at day 7 in the control rats but it was significantly increased from day 2 in the diabetic rats (320 +/- 52.9 ng/day at day 2 and 298 +/- 18.4 ng/day at day 7), while in the insulin-treated rats it was significantly less than that in the diabetic rats (134 +/- 8.34 ng/day at day 2 and 220 +/- 15.2 ng/day at day 7). Since the kidney is the main source of urine EGF and EGF has been shown to induce renal growth both in vitro and in vivo, we conclude that EGF may have initiated renal hypertrophy in diabetic rats.