One potential pathway by which depression may impact health is through modulation of immune function. Depressed individuals have been shown to display reductions in measures of cellular immune competence as well as elevated markers of systemic inflammation. The current study assessed the in vitro production of proinflammatory cytokines IL-6, IL-1beta, and TNF-alpha by peripheral blood mononuclear cells (PBMCs) in response to mitogen stimulation within a community-based sample of 79 midlife women. Results indicate that midlife women with higher levels of depressive symptoms (as assessed with the Center for Epidemiologic Studies Depression scale) and greater body mass index (BMI) displayed diminished production of IL-6, IL-1beta, and TNF-alpha by stimulated PBMCs, as compared with their less-depressed counterparts. These relationships remained after controlling for such health-related variables as age, recent sleep disruption, physical activity level, and self-reported medical history. In contrast, depressive symptoms were not significantly associated with circulating levels of the same proinflammatory cytokines (IL-6, IL-1beta, and TNF-alpha) obtained from serum samples available for a subset of 62 of the study participants. Moreover, circulating proinflammatory cytokine levels were not significantly associated with the in vitro proinflammatory cytokine production outcomes. Further research is needed to clarify the clinical significance of the current study findings, and the extent to which in vitro tests of stimulated proinflammatory cytokine production are associated with other measures of cellular immune function and/or circulating markers of systemic inflammation obtained across various study populations.