Ovine prolactin (PRL), a pituitary hormone, which has been shown to modulate a variety of T-cell immune responses, was tested for its capacity to elevate the respiratory burst and phagocytosis of peritoneal macrophages from three strains of young and aging mice following i.p. injection. The results were as follows. (a) PRL was found to enhance superoxide anion (O2-) generation and hydrogen peroxide (H2O2) release from macrophages removed from 2-3 months old young male and young female mice of the C3H/HeN, BALB/c and Swiss Webster (SW) strains. (b) PRL also increased the respiratory burst of aging mice of C3H/HeN (14-15 months old) and BALB/c (20-22 months old), but not the aging (13-15 months old), outbred, SW strain. (c) PRL-induced total H2O2 release was greater in young than aging mice, C3H/HeN and BALB/c mice, although the fold increase was similar; however, O2- generation was similar between young and aging mice of these strains. In SW mice, both O2- generation and H2O2 release were higher in young than in aging mice. (d) A statistically significant gender related difference was observed only in the H2O2 assay where young male BALB/c mice responded more strongly than young females. (e) Finally, phagocytosis of Candida albicans by macrophages from C3H/HeN mice was enhanced by PRL, with no demonstrable differences among young male, young female and aging male mice.