We examined lymphocyte responses to mitogens [phytohemagglutinin (PHA), concanavalin A, pokeweed] in spouse caregivers of persons with Alzheimer's disease (n = 82; mean age = 69.4) and noncaregiver spouses (n = 83) group matched on age and gender. Data were collected at study entry (T1) and 15-18 months later (T2). In men (n = 52), a depressed mood factor was negatively related to all mitogen responses at T1 and PHA at T2. Loneliness was the most important variable in the depressed mood factor. No relationships occurred in women (n = 113). At T2 an anger expression factor (anger-out--anger-control) was negatively related to all mitogen responses in caregivers. Anger-out was the most important variable for anger expression. Depressed mood at T1 predicted residualized changes in PHA at T2 in men. In conclusion, men with higher depressed mood and caregivers with higher anger expression may be at risk for lower proliferation responses.