During the manned lunar mission of Apollo 16, a study was undertaken to obtain more definitive information on human caloric requirements of prolonged exposure to weightless flight. Observations were made of immediate pre- and postflight body mass, total body water and exchangeable potassium. Continuous inflight recording of nutrient intake was achieved and partial metabolic excretory data were obtained. During weightlessness, the three crew members lost body water and adipose tissue. Caloric requirements calculated from these deficits proved to be different from those estimated prior to flight on the basis of body weight and age. The problem of predicting the metabolic cost of spaceflight is discussed.