In previous cross-sectional studies on Swiss mouse populations we have shown that at the same chronological age, animals that take longer to explore a simple T-maze (slow mice) are hyper-emotional and show an impairment of the immune system than those which quickly explore the maze (fast mice). Therefore, we have proposed that the slow mice are a model of prematurely aging mice (PAM). In the present work we have carried out a longitudinal study of age-dependent changes in key functions of phagocytic cells (peritoneal macrophages) such as phagocytosis and superoxide anion production in both male and female Swiss (outbred strain) and BALB/c (inbred strain) PAM and non-prematurely aging mice (NPAM). Gender differences were found showing the females better phagocytic and digestion capacities with concomitant longer life span. The PAM showed an impaired phagocytosis capacity and intracellular superoxide anion production as well as an increase of its extracellular production as compared to NPAM, which could be related to the shortened life span of those animals in both sexes and strains.