The aim of this study is to investigate the efficacy of a structured intervention program in emotional and physical states of family caregivers for elderly. This program is a series of five weekly 90-minute sessions including psycho-education, problem-solving techniques, and relaxation training. Subjects were 56 primary caregivers looking after relatives with dementia or disability at home. Psychological inventories, i.e., Profile of Mood States (POMS) and General Health Questionnaire30 (GHQ-30) were administered at the period of 4 weeks before, pre-, post-intervention, and 2 months after intervention. They were taken a blood sample to measure natural killer (NK) cell activity at the 4 weeks before, pre-, and post-intervention. In the waiting list control group, there was no change in the POMS, the GHQ-30 and NK cell activity. The scores for depression, anger-hostility, tension-anxiety, confusion (POMS), and general illness, social dysfunction, anxiety and dysphoria, suicidal depression (GHQ-30) at the post-intervention decreased significantly when compared with pre-intervention scores. Moreover, there was persistence of the improvement during two months after intervention. Post-intervention NK cell activity was significantly higher than the pre-intervention. These results indicated that our program was effective in managing the stress of family caregivers.