We examined peak and reserve cardiovascular function and skeletal muscle oxygenation during unilateral knee extension (ULKE) exercise in five heart transplant recipients (HTR, mean +/- SE; age: 53 +/- 3 years; years posttransplant: 6 +/- 4) and five age- and body mass-matched healthy controls (CON). Pulmonary oxygen uptake (Vo(2)(p)), heart rate (HR), stroke volume (SV), cardiac output (Q), and skeletal muscle deoxygenation (HHb) kinetics were assessed during moderate-intensity ULKE exercise. Peak exercise and reserve Vo(2)(p), Q, and systemic arterial-venous oxygen difference (a-vO(2diff)) were 23-52% lower (P < 0.05) in HTR. The reduced Q and a-vO(2diff) reserves were associated with lower HR and HHb reserves, respectively. The phase II Vo(2)(p) time delay was greater (HTR: 38 +/- 2 vs. CON: 25 +/- 1 s, P < 0.05), while time constants for phase II Vo(2)(p) (HTR: 54 +/- 8 vs. CON: 31 +/- 3 s), Q (HTR: 66 +/- 8 vs. CON: 28 +/- 4 s), and HHb (HTR: 27 +/- 5 vs. CON: 13 +/- 3 s) were significantly slower in HTR. The HR half-time was slower in HTR (113 +/- 21 s) vs. CON (21 +/- 2 s, P < 0.05); however, no significant difference was found between groups for SV kinetics (HTR: 39 +/- 8 s vs. CON 31 +/- 6 s). The lower peak Vo(2)(p) and prolonged Vo(2)(p) kinetics in HTR were secondary to impairments in both cardiovascular and skeletal muscle function that result in reduced oxygen delivery and utilization by the active muscles.