OBJECTIVE: This study investigated whether altruistic social interest behaviors such as engaging in helping others were associated with better physical and mental health in a stratified random sample of 2016 members of the Presbyterian Church throughout the United States. METHODS: Mailed questionnaires evaluated giving and receiving help, prayer activities, positive and negative religious coping, and self-reported physical and mental health. RESULTS: Multivariate regression analysis revealed no association between giving or receiving help and physical functioning, although the sample was highly skewed toward high physical functioning. Both helping others and receiving help were significant predictors of mental health, after adjusting for age, gender, stressful life events, income, general health, positive and negative religious coping, and asking God for healing (R2 =.27). Giving help was a more important predictor of better reported mental health than receiving help, and feeling overwhelmed by others' demands was an independent predictor of worse mental health in the adjusted model. Significant predictors of giving help included endorsing more prayer activities, higher satisfaction with prayer life, engaging in positive religious coping, age, female gender, and being a church elder. Frequency of prayer and negative religious coping were not related to giving help. CONCLUSIONS: Helping others is associated with higher levels of mental health, above and beyond the benefits of receiving help and other known psychospiritual, stress, and demographic factors. The links between these findings and response shift theory are discussed, and implications for clinical interventions and future research are described.