It is generally believed that cross bridges account for >50% of the total ATP consumed by skeletal muscle during contraction. We investigated the effect of N-benzyl-p-toluene sulfonamide (BTS), an inhibitor of myosin ATPase, on muscle force production and energy metabolism under near-physiological conditions (50-Hz stimulation frequency at 30 degrees C results in 35% of maximal force). Extensor digitorum longus muscles from mice were isolated and stimulated to perform continuous isometric tetanic contractions. Metabolites of energy metabolism were analyzed with fluorometric techniques. ATP turnover was estimated from the changes in phosphocreatine (PCr), ATP, and lactate (-2DeltaATP - DeltaPCr + [1.5Deltalactate]). During contractions (2-10 s), BTS decreased force production to approximately 5% of control. Under these conditions, BTS inhibited ATP turnover by only 18-25%. ATP turnover decreased markedly and similarly with and without BTS as the duration of contraction progressed. In conclusion, cross bridges (i.e., actomyosin ATPase) account for only a small fraction (approximately 20%) of the ATP consumption during contraction in mouse fast-twitch skeletal muscle under near-physiological conditions, suggesting that ion pumping is the major energy-consuming process.