Serum somatomedin A was significantly reduced after 3 days of fasting in rats with a mean decrease of 23.6 +/- 2.4% (N = 18) of initial values. Re-feeding for one day produced a definite increase in somatomedin A, with a rise in body weight. When re-fed isocalorically for 21 days with diets of different quality, a low protein diet led to smaller increases in both serum somatomedin A and body weight in comparison to those of control-, high-protein- and high fat-diets (P < 0.001). There is a positive correlatin between the increase in body weight and serum somatomedin A levels (N = 70, r = 0.71, P < 0.001). The effect of growth hormone on somatomedin generation was abolished in hypophysectomized rats fed with low-protein diet. Our study suggests that protein in the diet is important for the generation of somatomedin A, which is necessary for normal growth.