SUMMARYWe investigated sprint performance and running economy of a unique 'mini-muscle' phenotype that evolved in response to selection for high voluntary wheel running in laboratory mice (Mus domesticus). Mice from four replicate selected (S) lines run nearly three times as far per day as four control lines. The mini-muscle phenotype, resulting from an initially rare autosomal recessive allele, has been favoured by the selection protocol, becoming fixed in one of the two S lines in which it occurred. In homozygotes, hindlimb muscle mass is halved, mass-specific muscle oxidative capacity is doubled, and the medial gastrocnemius exhibits about half the mass-specific isotonic power, less than half the mass-specific cyclic work and power, but doubled fatigue resistance. We hypothesized that mini-muscle mice would have a lower whole-animal energy cost of transport (COT), resulting from lower costs of cycling their lighter limbs, and reduced sprint speed, from reduced maximal force production. We measured sprint speed on a racetrack and slopes (incremental COT, or iCOT) and intercepts of the metabolic rate versus speed relationship during voluntary wheel running in 10 mini-muscle and 20 normal S-line females. Mini-muscle mice ran faster and farther on wheels, but for less time per day. Mini-muscle mice had significantly lower sprint speeds, indicating a functional trade-off. However, contrary to predictions, mini-muscle mice had higher COT, mainly because of higher zero-speed intercepts and postural costs (intercept-resting metabolic rate). Thus, mice with altered limb morphology after intense selection for running long distances do not necessarily run more economically.