Background-Skeletal muscle assist (SMA) may be limited by loss of power, slowing of contraction and relaxation, and atrophy of the transformed latissimus dorsi muscle (LD). Clenbuterol (clen), a  2 -adrenergic receptor agonist, was used to improve the performance of trained skeletal muscle in sheep. Methods and Results-The following 4 groups were used: A (nϭ6), untrained controls; B (nϭ6), left LD progressively transformed toward a slow-twitch and fatigue-resistant phenotype by electrical stimulation over 12 weeks (2.5 to 5 V, 240-sec pulse duration, 35 Hz, 3 to 6 pulses per burst, and up to 40 bursts per minute); C (nϭ6), clen-treated (0.5 mg/kg SC) for 12 weeks; and D (nϭ6), clenϩtrained. In a terminal experiment, the mobilized LD was wrapped around a rubber aorta of a mock circulation and stimulated to contract 40 times per minute. Group A had an initial mean pressure augmentation (⌬P) of 24.6 mm Hg and stroke power of 2.28 W/kg, but both fell to Ͻ20% of their original values by 15 minutes because of fatigue (PϽ0.005). Group B was fatigue-resistant, with a ⌬P and stroke power at 60 minutes of 13 mm Hg (70% of initial) and 0.34 W/kg (39% of initial), respectively. The performance of group C was similar to that of controls. In group D, however, the muscles were stronger at all time points than in B, with a ⌬P of 23 mm Hg and stroke power of 2.66 W/kg at 60 minutes (PϽ0.01). The speeds of contraction (ϩdP/dt:⌬P) and relaxation (ϪdP/dt:⌬P) were significantly greater in group D than B.Protein analyses showed group D to have only a trend toward greater abundance of the fast isoforms of myosin heavy chain and sarcoplasmic reticulum Ca