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Nausea and vomiting are common side effects of chemotherapy in adult and pediatric patients. Even with standard antiemetic therapy, a significant number of patients continue to experience acute and delayed symptoms. When used in combination with standard antiemetic therapy, a new class of antiemetics, the neurokinin-1 (NK-1) receptor antagonists, have been shown to improve both acute and delayed nausea and vomiting in adults. In this report, we describe the NK-1 receptor antagonist aprepitant in two adolescent patients receiving highly emetogenic chemotherapy who had experienced refractory nausea and vomiting with previous chemotherapy courses. The addition of aprepitant to the antiemetic regimen in the patients resulted in significant subjective improvement in nausea and vomiting as well as quality of life. These results in our adolescent patients are promising, but there is a need for well-designed studies to determine the efficacy, dosing, and safety of aprepitant in children of all ages. © 2005 Wiley-Liss, Inc.