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This cross-sectional study investigated whether active and avoidance coping methods were differentially related to immune function depending on stress level. Perceived stress and coping method were assessed in 173 healthy older adults and related to the number and percentage of CD3+, CD4+, and CD8+ T lymphocytes as well as the proliferative response of peripheral blood leukocytes to phytohemagluttinin (PHA) and concanavalin A (Con A). Both active and avoidance coping significantly interacted with perceived stress on proliferative responses to both mitogens. Higher levels of active coping were significantly related to a more vigorous proliferative response to PHA and Con A, particularly at high stress levels. At low stress levels, active coping was not significantly related to proliferative responses, whereas avoidance coping was significantly associated with a greater proliferative response to Con A. These results suggest that the relationships between certain coping methods and immune function depend on perceived stress level.