Providing long-term care for a demented relative profoundly affects caregivers' lives. We assessed changes in depression, immune function, and health in 69 spousal caregivers who had already been caregiving for an average of five years and 69 sociodemographically matched control subjects. Between the initial sample ("intake") and the follow-up data collected an average of 13 months later, caregivers showed decrements relative to controls on three measures of cellular immunity. Caregivers also reported significantly more days of infectious illness, primarily upper respiratory tract infections. Caregivers had a much greater incidence of depressive disorders than controls, with 25% of caregivers meeting syndromal criteria at intake and 32% at follow-up, compared with no cases among controls at intake and 6% at follow-up. Caregivers who reported lower levels of social support at intake and who were most distressed by dementia-related behaviors showed the greatest and most uniformly negative changes in immune function at follow-up.