The objective of this study was to investigate food restriction-related changes in several indices of immune competence in young (11 wk old) and adult (33 wk old) female lean (+/?) and obese (ob/ob) C57BL/6J mice. Body weight accumulation, tail length accretion and organ weights were more severely curtailed by food restriction in obese mice than in lean mice. Tail collagen denaturation time increased with age, although the magnitude was greater in obese mice, and this change was minimized by food restriction. Splenocyte mitogen responses were generally not altered with age in lean or obese mice, whereas food restriction augmented these responses in lean mice while having no effect or reducing them in obese mice. The concanavalin A and phytohemagglutinin responses of splenocytes from young and adult obese mice were greater than those for lean mice, whereas the bacterial lipopolysaccharide response was elevated only in adult obese vs. lean mice. Flow cytometric analysis of splenocytes revealed an increase in Thy-1+ cells with food restriction vs. freely fed obese and lean mice, with a proportional decrease in Ig+ cells. Percentages of CD4+ and CD8+ cells increased with food restriction in both lean and obese mice. These results suggest that genetic obesity largely eliminates the immunopotentiating effects of food restriction, although the rate of "aging" may be reduced by food restriction.