Weight gain, a common side effect among breast cancer patients receiving adjuvant chemotherapy, may decrease quality of life and impair survival. Weight gain during treatment is a well-known problem and has been studied by many investigators. However, few controlled studies have been conducted to determine reasons to explain this apparent energy imbalance. An exploratory study was undertaken to quantitate potential changes in energy intake and specific components of energy expenditure in breast cancer patients receiving adjuvant chemotherapy. The research hypothesis was that a reduction in resting metabolic rate (RMR) would be observed during the period in which women received adjuvant chemotherapy. Twenty premenopausal patients with stage I or II breast cancer and receiving cyclophosphamide+doxorubicin+5-fluorouracil; cyclophosphamide +methotrexate+5-fluorouracil+/-doxorubicin; doxorubicin +cyclophosphamide+/-leucovorin; or methotrexate+5-fluorouracil +leucovorin chemotherapy were recruited. RMR, diet-induced thermogenesis, energy intake, physical activity, and body composition were assessed before the initiation and throughout the course of therapy. Complete data on 18 subjects suggest that RMR decreased significantly from baseline to midtreatment (P = 0.02) and rebounded to levels similar to those at baseline on completion of chemotherapy. Overall, levels of physical activity and energy intake also decreased significantly during treatment compared with baseline levels (P = 0.04 and P = 0.03, respectively). These findings suggest that chemotherapy provokes many significant changes in body composition and metabolic requirements. Additional research in this area will provide valuable insight into creating optimal interventions to curb weight gain in women with breast cancer.