Evidence from clinical and experimental studies has shown that placebos influence mood and behavior, that endogenous opioids are involved in the placebo effect, and that the endogenous opioid system is related to psychological events. Recent studies have also demonstrated that the endogenous opioid system is closely connected with other neurotransmitter systems in the brain. The author suggests that the interaction between the endogenous opioid system and different neurotransmitter systems in the brain mediates the placebo effect on mood and behavior of both healthy and sick people.