Kidney growth after induction of experimental diabetes in rats was compared to compensatory renal growth in response to unilateral nephrectomy. After 4 days of diabetes, kidney weight had increased from 816 +/- 21 mg (SEM) to 940 +/- 42 mg (15%). In insulin-treated diabetic rats kidney weight was unchanged at the end of the study, namely 828 +/- 15 mg. In unilaterally nephrectomised rats kidney weight increased from 840 +/- 20 mg (SEM) to 1050 +/- 60 mg during 4 days (24%). We observed increased kidney content of somatomedin C in both diabetic and uninephrectomized rats. In untreated diabetic rats it was maximal after 48 h, with an increase of 77% (3469 +/- 312 ng/g (SEM) versus 1961 +/- 173 ng/g). After 4 days the somatomedin C content had returned to initial levels. In insulin-treated rats somatomedin C content did not increase during the observation period. The somatomedin C content of the remaining kidney after unilateral nephrectomy was maximal after 24 h with an increase of 58% (from 1340 +/- 203 ng/g (SEM) to 2122 +/- 214 ng/g). The somatomedin C content returned to normal at day 4. Serum somatomedin C declined insignificantly in diabetic animals during the experimental period, but a significant decrease (p less than 0.02) was found in uninephrectomized rats. This study demonstrates that kidney somatomedin C peaks during the first or second day after uninephrectomy or induction of diabetes, respectively, and that insulin treatment sufficient to prevent kidney growth abolishes the increase. These similar rapid initial hypertrophies/hyperplasies may thus be dependent on local somatomedin C formation.