The mechanisms responsible for immediate adjustments in cardiac output at onset of exercise, in the absence of neural drive, are not well defined in heart transplant (HT) recipients. Seven male HT recipients (mean ± SD 57 ± 6 years) and 7 age-matched sedentary normal control subjects (mean age 57 ± 5 years) performed constant load cycle exercise at 40% of peak power output (Watts). Cardiac output and plasma norepinephrine were determined at rest and every 30 seconds during the first 5 minutes of exercise and at minutes 6, 8, and 10. All subjects were admitted to the General Clinical Research Center for determination of plasma volume. After 3 days of equilibration to a controlled and standardized diet, plasma volume was measured using a modified Evans Blue Dye (T-1824) dilution technique. Heart rate at rest was higher in the HT group (105 ± 12 vs 74 ± 6 beats/min), but during submaximum exercise, heart rates in the control group increased more rapidly (p ≤0.05) and to a greater magnitude (54 ± 7% vs 17 ± 4% above rest). Stroke volume at rest was lower in HT recipients (45 ± 4 vs 68 ± 9 ml) but was significantly augmented immediately after onset of exercise (30 seconds) and the relative increase was greater than controls at peak exercise (61% vs 38% greater than baseline). Cardiac output at rest was within the normal range in both groups (4.58 ± 0.27 vs 4.94 ± 0.40 L/min). Relative increases in cardiac output were similar (p ≥0.05) for the HT (106 ± 12%) and control groups (97 ± 10%). Plasma norepinephrine did not become significantly greater than resting values until approximately 4 minutes after onset of exercise in both groups. Blood volume, normalized for body weight, was 12% greater in the HT group. Thus, HT recipients with expanded blood volume (12%) augment stroke volume immediately after the onset of exercise. Plasma norepinephrine levels contribute negligibly to the rapid adjustment in cardiac output. Rather, we speculate that abrupt on-transit increases in stroke volume are due to augmented venous return, secondary to expanded blood volume.