Objective: The objective of this study was to examine how the chronicity of stress affects psychological stress-responses, depressive symptoms, and "in vivo" immunocompetence in spouses of women with metastatic breast cancer. Methods: Participants were 34 spouses of breast cancer patients. Their wives had been living with a diagnosis of recurrence metastatic breast cancer for a mean of 2.3 (SD = 3.6) years. Stress chronicity was defined as the length of time since the partner's diagnosis with metastatic breast cancer. Self-reports of psychological stress responses (IES) and depression (CES-D) were taken, and in vivo immunocompetence was assessed by delayed type hypersensitivity (DTH) responses to skin test antigens. Results: Clinically significant levels of depressive symptoms (CES-D greater than 16) were reported in 15% of participants. Suppression of the DTH response was greater in men who had been living longer with an ill spouse (Spearman r = -0.39, p = 0.011), those who reported more psychological stress (r = 0.37, p = 0.16), and those who had more severe depressive symptoms (r = -0.28, p = 0.054). There was no association between the duration of disease and spouse's depression, however, those who had been living longer with an ill partner reported less psychological stress. Conclusions: This study substantiates a relationship between depression and cell-mediated immunity in spouses with a seriously ill partner. Further, these results suggest that the duration of stress is an important factor of stress-induced immunosuppression. They also highlight the potential importance of interventions to alleviate depression among family members of cancer patients. (Contains 1 table.)