It is demonstrated that cell proliferation in response to mitogens, natural killer cell (NK) activity, and macrophage functioning of mice may be influenced by either a neurogenic stressor (footshock) or a psychogenic stressor (exposing the mouse to a predator, namely a rat). The nature and magnitude of the immune changes, however, varied across three strains of mice (BALB/cByJ, C57BL/6ByJ, and CD-1), differing in reactivity to stressors and also as a function of the type of stressor employed. While footshock reduced mitogen-stimulated B-cell proliferation in BALB/cByJ mice, it had the opposite effect in the CD-1 strain. Exposure to the predator, however, had little effect in any of the strains. Macrophage activity and NK cytotoxicity were reduced in response to both stressors in a strain-dependent fashion. Plasma corticosterone in response to footshock was greater in BALB/cByJ than in C57BL/6ByJ mice; however, the strain difference was not evident in response to the psychogenic stressor. It is suggested that analyses of stressor effects on immune functioning need to consider the specific strain/species employed, the particular immune parameters being examined, and the nature of the stressor employed.