The purpose of this study was to determine the reliability and validity of an instrument that measures both spirituality and religiousness, to examine the relation between spirituality and religiousness and important health outcomes for people living with HIV and to examine the potential mediators of these relations. One aim was to determine whether subscales of spirituality, religiousness, or both would be independently related to long survival in people living with AIDS. The Ironson-Woods Spirituality/Religiousness (SR) Index is presented with evidence for its reliability and validity. Four factors were identified on the Ironson-Woods SR Index (Sense of Peace, Faith in God, Religious Behavior, and Compassionate View of Others). Each subscale was significantly related to long survival with AIDS. That is, the long-term survivor (LTS) group (n = 79) scored significantly higher on these factors than did the HIV-positive comparison (COMP) group (n = 200). Long survival was also significantly related to both frequency of prayer (positively) and judgmental attitude (negatively). In addition, the Ironson-Woods SR Index yielded strong and significant correlations with less distress, more hope, social support, health behaviors, helping others, and lower cortisol levels. The relation between religious behavior and health outcomes was not due to social support. Further analyses were conducted, which identified urinary cortisol concentrations and altruistic behavior as mediators of the relation between SR and long survival.