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Several studies have shown that patients' expectancies for the development of nausea following chemotherapy are robust predictors of that treatment-related side effect, and some studies have shown that interventions designed to influence expectancies can affect patients' reports of symptoms. In this randomized, multicenter, Community Clinical Oncology Program trial, we investigated the effect of an expectancy manipulation designed to reduce nausea expectancy on chemotherapy-induced nausea in 358 patients scheduled to receive chemotherapy treatment. Patients in the intervention arm received general cancer-related educational material plus specific information about the efficacy of ondansetron, specifically designed to diminish nausea expectancy. Patients in the control arm received only the general cancer-related educational material. Nausea expectancy was assessed both prior to and following the educational intervention. We observed a significant reduction in nausea expectancy in the intervention group (P=0.024) as compared to the control group (P=0.34). In the intervention group, patients' expectations of nausea assessed prior to the intervention correlated significantly with average nausea (r=0.27, P=0.001), whereas nausea expectancy assessed following the intervention did not (r=0.1, P=0.22). Although the expectancy manipulation reduced patients' reported expectations for the development of nausea, the occurrence of nausea was not reduced. Furthermore, post-intervention nausea expectancy compared to pre-intervention expectancy was less predictive of subsequent nausea. Explanations for these findings include the possibility that the expectancy manipulation was not strong enough, and the possibility that changing nausea expectancies does not change occurrence of nausea.