Male rabbits were injected daily for 14 days with prednisone 2 mg/kg. The content and metabolism of collagen and glycosaminoglycans, the content of RNA, DNA, fat and water and the 125I-albumin permeability were investigated in the skin and in the intima-media layer of the aorta. A saline injected group served as control. Since prednisone induced a decrease in body weight, a starvation group with a similar weight loss was included. Following injections of prednisone the protocollagen proline hydroxylase activity, 0.45 m NaCl soluble hydroxyproline, total hydroxyproline, dialysable 14C-hydroxyproline and non-dialysable 14C-hydroxyproline fractions were reduced in the skin. In the aorta, only the total 14C-hydroxyproline synthesis was decreased. Furthermore there was a decrease in 14C-proline incorporation and the alpha-amino nitrogen content in the skin as well as a decrease in the RNA content in the skin and the aorta. It is concluded that prednisone acts mainly anti-anabolically on the metabolism of collagen and that this effect is part of a general inhibition of the protein synthesis. The sensitivity of the connective tissue of different organs to prednisone varies. Following prednisone treatment the 35S-sulphate incorporation into glycosaminoglycans was decreased in the skin as well as in aorta. However, this did neither affect the concentration nor the total amount of the different glycosaminoglycans – except for a decrease in chondroitin-4/6-sulphate in aorta. These findings probably indicate that prednisone inhibits the synthesis as well as the catabolism of the glycosaminoglycans. The skin and aorta reacted almost similarly. Prednisone raised the tissue to serum ratio of 125I-albumin. This may reflect changes in filtration and/or diffusion rates of albumin through the aortic endothelium and media. Finally, a decrease in body weight following starvation influenced the metabolism of collagen somewhat similar to the effect of prednisone, whereas the effects on the glycosaminoglycans differed.