The in vivo synthesis of the renal glomerular basement membrane (GBM) collagen was studied in normal, hypophysectomized (hypox), diabetic, and growth-hormone (GH)-treated diabetic rats, using tritiated proline (L[2,3,3H]proline) as a radioisotopic precursor. After the injection of tritiated proline, all groups of rats were sacrificed at various time intervals and the specific activities of proline and hydroxyproline of GBM were determined, the latter being used as a measure of GBM collagen synthesis. A significant decrease in both proline and hydroxyproline specific activities were observed in GBM of hypox rats at all periods of study. Administration of GH to hypox rats returned the GBM collagen synthesis to normal. Diabetic GBM had higher proline and hydroxyproline specific activities when compared to normal rats. Treatment of diabetic rats with GH for 10 days further increased both proline and hydroxyproline specific activities when compared either to diabetic or normal rats treated with GH. The activity of glucosyltransferase, an enzyme involved in the biosynthesis of the disaccharide unit of GBM collagen was found to be decreased in glomeruli of hypox rats. In contrast, the activity of N-acetyl-beta-glucosaminidase, a glycoprotein-degrading enzyme, was found to be significantly increased in hypox rats. GH treatment restored both enzyme activities to normal. The results of the present study show that GBM collagen synthesis is decreased in hypox rats and increased in diabetic rats. GH treatment not only normalized GBM collagen synthesis in hypox rats but also caused significant increase in diabetic rats. This suggests that the renal GBM metabolism is influenced by GH, and this may be of particular significance in view of GH involvement in diabetic microvascular complications.