Background: Patients with chronic heart failure demonstrate several skeletal muscle abnormalities. The underlying mechanisms are unclear. After cardiac transplantation, cardiac function is restored, but exercise capacity is still impaired. Aim: To evaluate the influence of cardiac transplantation on skeletal muscle fibre composition, fibre area and capillarization as well as muscle enzymes, lactate, thigh muscle area and strength. Methods: Ten patients were longitudinally investigated before, 1-3 and 6-9 months after transplantation. Ten healthy individuals served as controls. A biopsy from the lateral vastus muscle was obtained and the thigh muscle area was measured with computed tomography. Muscle strength in the knee extensors and exercise capacity were also evaluated. Results: Muscle lactate was elevated in patients vs. controls (3.6+/-3.0 vs. 1.5+/-0.7 mmol/kg wet wt., P=0.037), and decreased to normal (1.4+/-0.3 mmol/kg wet wt., P=0.038) after transplantation. Citrate synthase activity was decreased in patients (5.6+/-1.5 μmol/g wet wt./min) vs. controls (8.1+/-1.6 μmol/g wet wt./min, P=0.0018), and did not change post transplantation. Patients had decreased number of capillaries in contact with each fibre vs. controls (2.6+/-0.5 vs. 3.5+/-1.0, P=0.039) which persisted post transplantation. Exercise capacity increased after transplantation (74+/-22 vs. 118+/-26 W, P=0.0002), whereas muscle strength did not improve significantly. Conclusion: The persisting intrinsic abnormalities in skeletal muscle after cardiac transplantation may contribute to the impaired exercise capacity observed in cardiac transplant recipients.