We have studied the effect of a calorie-restricted diet on the growth of young rats and on serum levels of GH, somatomedins (insulin-like growth factors I and II), total T4 and T3, free T4 index, and total corticosterone. Experimental rats consumed the same quantities of protein and carbohydrate as control animals, but less fat, so that their calorie intake was approximately 76% that of controls. The mean (+/- SEM) GH level in the experimental group (78 +/- 21 ng/ml) was not significantly different from that in the control group (89 +/- 31 ng/ml). In contrast, serum total insulin-like growth factor and insulin-like growth factor IGF-I, while not correlated with serum GH, were significantly correlated with age and body weight (r = 0.93 and r = 0.69, respectively; P less than 0.01). The levels of these somatomedins in the calorie-restricted rats were significantly lower than those in their age-matched, but not weight-matched, controls after approximately 2 weeks of study. Serum T4, T3, and free T4 index were all significantly reduced in the experimental animals and may represent an adaptive response to calorie restriction. Serum corticosterone levels in the experimental and control rats were essentially identical. In this study, by restricting calorie intake we have compromised the ability of growing rats to use dietary protein anabolically, creating a useful model to examine in some detail nutritional influences on growth and the growth-promoting endocrine system.