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Regional infusion of antineoplastic agents at the time of surgery or during a procedure provides a unique opportunity for oncology nurses and other nurses and technicians to develop cutting-edge policies and procedures for safe administration. The administration of these agents occurs in nontraditional clinical settings of the National Cancer Institute (NCI) and National Institutes of Health, including the operating room and the interventional radiology suite. This article (part I) provides a summary of the regional antineoplastic therapy clinical studies currently under way in the surgery branch of the Center for Cancer Research at NCI. Part II (see page 345) provides an overview of the nursing implications of administering the agents in these nontraditional clinical settings.