The aim of this investigation was to study how the known dependence of working efficiency on pedaling frequency is influenced by the work load as well as by physical fitness. Oxygen uptake, CO2 output, ventilation, heart rate, and lactate concentration in capillary blood from the earlobe were determined at varying combinations of work loads and pedaling rates in road-racing cyclists and medical students. Respiratory exchange ratio, consumption of energy, gross efficiency, net efficiency, and delta efficiency (delta work rate/delta metabolic rate) were calculated. All parameters showed a nonlinear dependence on pedaling frequency. The lowest oxygen uptake and the highest efficiency shifted to higher frequencies with increasing work load. Delta efficiency increased with rising pedaling frequency. Differences of VO2 and efficiencies between trained and untrained subjects were only small. Most effects can be explained by variations in leg movement frequency and recruitment of muscle fibers. There is evidence that racing cyclists chose pedaling rates yielding optimal efficiency at any load.