The purpose of this analysis was to explore strain and depression among family caregivers of persons receiving chemotherapy for cancer using the Pearlin Stress Process Model. Seventy-five family caregivers of persons receiving chemotherapy participated, completing the Caregiver Strain Index and the Depression Subscale of the Profile of Mood States within 3 weeks of the initiation of chemotherapy. Hierarchical regression analyses indicated that 44% of the variance in strain and 40% of the variance in depression were explained by the antecedent variables of caregiver age and gender, patient age and gender, patient functional status, the presence of recurrent disease, perceived efficacy of coping strategies, and perceived adequacy of social support. Further analysis aimed at delineating the mechanisms through which coping and social support operate in the model found no evidence for a moderating or stress-buffering effect. However, coping mediated the relationship between strain and depression and social support mediated the relationship between functional status and depression.