Increasing numbers of American families seek complementary and alternative medical care (CAM) for their children; at the same time health care organization and financing are undergoing radical changes. The combination of these factors provides a powerful incentive for research on the effectiveness and safety of CAM therapies and their role in treating children. This article describes a rationale, spectrum, priorities, and methodologies for a research agenda in holistic pediatrics. The top priorities are clinical research projects addressing the safety and effectiveness of alternative therapies used for vulnerable children suffering from serious illnesses. Additionally, major research questions involve the impact of the various definitions such as "alternative," "complementary," "folk," "integrative," and "holistic" medicine on perceptions of health care, professional education, and funding of products and services. Research efforts in alternative therapies need to address explicitly the tremendous heterogeneity between and among the practices, beliefs, and providers of professional and lay services. Qualitative ethnographic research is needed to understand the consequences of diverse explanatory models and meanings of health and illness for patient-provider communication, adherence with professional recommendations, and satisfaction with care. Health services researchers need to address questions related to the epidemiology of CAM practices, health manpower issues, practice characteristics and the process and content of health care and how discoveries about CAM care may enhance the quality of mainstream health services. A rationale is provided for prioritizing certain conditions and therapies within these efforts.