Fifty-four pediatric cancer patients were studied to determine the relative efficacy of two forms of behavioral intervention for reducing chemotherapy-related distress. Following baseline assessment, subjects were randomly assigned to receive either hypnosis, non-hypnotic distraction/relaxation, or attention placebo (control) during the subsequent identical chemotherapy course. Observational and interview measures of anticipatory and postchemotherapy nausea, vomiting, distress, and functional disruption served as outcome data. Results indicated that treatment condition was the single best predictor of change from baseline to intervention, with children in the hypnosis group reporting the greatest reduction of both anticipatory and postchemotherapy symptoms. The cognitive distraction/relaxation intervention appeared to have a maintenance effect in which symptoms did not get much worse or much better, while children in the control group had symptoms that consistently became worse over time. Emetic potential of the chemotherapy and the prophylactic use of antiemetics each appeared to contribute to the overall severity of symptoms. While the efficacy of hypnosis in the management of chemotherapy distress is supported, the complexities of interacting biologic and psychologic factors are highlighted.