Objectives: Calorie restriction has been associated with anorexia in growing individuals, but the mechanisms involved are not known. Also, the effects of carbohydrates and lipid restriction in growing individuals were not studied. The aim of this study was to determine whether 66% calorie restriction (lipids and carbohydrates) differentially affects growing rats of the Wistar or Lewis strains. Methods: Growing male Wistar and Lewis rats were subjected to 66% calorie restriction for 4 weeks. Plasma prolactin, growth hormone (GH), and adrenocorticotropic hormone (ACTH) levels were measured by specific radioimmunoassays. Likewise, lymphocytes from submaxillary lymph nodes were aseptically obtained to study absolute number of lymphocytes, cell surface markers (CD4+, CD8+, CD4+CD8+, B, and T cells), and proliferation. Results: The body weight gain was lower in Lewis than in Wistar rats and was blunted in both strains by calorie restriction. Wistar and Lewis rats exhibited differential patterns of plasma prolactin, ACTH, and GH levels as well as proliferative capacities of T and B cells and their distribution in the submaxillary lymph nodes. Calorie restriction increased plasma prolactin and ACTH levels in Lewis as compared with Wistar rats. However, the plasma GH levels were diminished in both strains of rats by calorie restriction. All changes in plasma prolactin ACTH and GH levels seemed to correlate with the modifications observed in the distributions of T and B subsets in the submaxillary lymph nodes as well as in their proliferative capacity. Conclusions: Calorie restriction differentially modifies the secretory patterns of prolactin, GH, and ACTH in Lewis and in Wistar rats. These changes may explain, at least in part, the associated modifications in the proliferative capacity of submaxillary lymph node lymphocytes and in their distribution.