Objective: The aim of our study is to determine the effect of a 30-day-period caloric restriction (CR) upon the immune response of rats and the influence of glutamine upon mononuclear cells proliferation and cytokine production., Methods: Male albino Wistar rats were submitted to CR receiving an amount of food equivalent to 50% of the mean amount consumed by the control animals. We measured the incorporation of [2-14C]-thymidine by lymphocytes obtained from the spleen and mesenteric lymph nodes, plasma glucose and glutamine concentration, as well as cytokine production by cultivated cells, in the presence of glutamine., Results: Rats submitted to CR presented reduced body weight (49%) and decreased splenic leukocyte number. CR led to a reduction in the proliferative response of lymphocyte. Spleenocytes from CR animals produced less gamma-interferon and interleukins 1, 4 and 10 in 48 h culture than did those from control rats. The same pattern is observed in cells obtained from the mesenteric lymph nodes. The addition of glutamine 2mM to the culture medium restored spleen and mesenteric lymph node cells' proliferative response and the production of interleukin 2 by cells obtained from the spleen and from the mesenteric lymph nodes., Conclusions: The present data reinforce that undernutrition decreases in vitro immune cell function and indicates that, in such circumstances, glutamine supplementation could reverse some of the changes observed in the functionality of cultured immune cells. The presence of the amino acid at physiological concentration, however, reinforces the diversion of the immune response towards a Th(1)-like response.