We examined the effects of energy restriction on immune response and also compared the effects of low fat (LF, 18.6 E%) and high fat (HF, 40.7 E%) diets during energy restriction on immunological parameters. Ten overweight women were fed the HF diet for 42 days (P1) to maintain their body weights. For the next 84 days (P2), the energy intake was reduced to 50% of the intake during P1 for all the women, five of them were fed the HF diet and the other five the LF diet. For the last 35 days of the study (P3), subjects remained on their respective diets, but the energy intake was increased to maintain BW to the level reached at the end of energy restriction. Serum concentrations of IgG, IgA, IgM, C3 and C4, numbers of lymphocytes and their subsets, blastogenesis of peripheral blood mononuclear cells cultured with phytohemagglutinin, concanavalin A and protein A were determined several times during the study. Delayed hypersensitivity skin (DHS) response to seven recall antigens was determined towards the end of each study period. None of the parameters studied were different between the HF and LF dietary groups. During energy restriction the subjects lost an average of 7 kg in the LF group and 9 kg in the HF group. Energy restriction caused a significant (P < 0.005) decrease in the serum concentration of IgG, IgA, C3, and the number of circulating natural killer (NK) cells. An increase in energy intake during P3 reversed some of the decreases caused by energy restriction, but the levels did not return to pre-restriction levels during these 35 days of refeeding adequate dietary energy. The numbers of circulating lymphocytes and their subsets with the exception of NK cells, serum levels of IgM and C4, and the DHS response monitored 48 h after the application of antigens were not affected by energy restriction. Health status of the women in our study did not seem to be compromised; however, it could be compromised under more drastic restrictions or with moderate restrictions in high risk subjects.