We evaluated the influence of continual estrogen replacement therapy (ERT) as presently practiced by postmenopausal women with conjugated estrogens and medroxyprogesterone acetate (MPA) on the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and cellular immunity. Thirty-nine postmenopausal women were evaluated (12 on no replacement, 14 on estrogen only, and 13 on estrogen and MPA). In the women receiving only conjugated estrogens, increased GH levels and decreased IGF-1 levels were found, which replicated previous research and probably reflected estrogen inhibition of hepatic IGF-1 production with a secondary increase in GH release because of reduced feedback inhibition. In women taking both MPA and estrogen, GH was increased and the previously observed estrogen induced decrease in IGF-1 levels was inhibited. In order to determine the influence of ERT on psycho-social stress-induced GH release, math (mental stress) and speech (social stress) challenges were utilized, and they produced significant increases in heart rate in all three groups. The heart rate following stress was significantly enhanced by estrogen replacement. These stressors also led to increased GH secretion in the women taking estrogen and MPA, but not in the other two groups. Gonadal steroids and GH can influence cellular immunity. We observed that ERT in both groups was associated with significantly enhanced lymphocyte responsiveness to the T-cell mitogens phytohemaglutinin (PHA) and Conconavalin A (Con A), and basal GH levels were correlated with the PHA response in the estrogen only group. ERT did not influence natural killer (NK) cell activity. We also found significant differences in the steady-state expression of latent Epstein-Barr virus (EBV) with increased antibody titers in the women in the estrogen only group and lower antibody titers in the MPA plus estrogen group. GH levels were correlated with EBV antibody titers in the estrogen plus MPA group. This study supports the hypothesis that GH and immune modulation can be influenced by ERT in postmenopausal woman. Given the extant literature on the immune-enhancing effects of GH, these data suggest that ERT may slow the decline of GH secretion with aging, an event that has been implicated in immunosenescence.