Exercise capacity in hypertrophic cardiomyopathy is thought to relate to elevated left atrial pressure as a consequence of impaired diastolic function, but this assumption has not previously been evaluated. Twenty-three patients with hypertrophic cardiomyopathy underwent hemodynamic assessment during symptom-limited maximal exercise with objective measurement of exercise capacity by respiratory gas analysis. Maximal oxygen consumption and anaerobic threshold were 28.1 +/- 7.5 and 21.5 +/- 6.1 ml/kg per min, respectively (the lower limit of reference range in our laboratory is 39 and 27 ml/kg per min, respectively). Maximal oxygen consumption was reduced in 11 of 13 patients who were in New York Heart Association functional class I and who denied limitation of exercise capacity and in all 10 patients who were in functional class II or III. Maximal oxygen consumption and anaerobic threshold were related to peak cardiac index (r = 0.650, p less than 0.001 and r = 0.459, p = 0.03, respectively) and to the increase in cardiac index on exercise (r = 0.677, p less than 0.001 and r = 0.509, p = 0.016, respectively), but not to cardiac index at rest, peak and rest pulmonary capillary wedge pressure, pulmonary capillary wedge pressure at an oxygen consumption of 15 ml/kg per min or the rise in pulmonary capillary wedge pressure on exercise. These findings are not consistent with the hypothesis that elevated left atrial pressure is the major determinant of exercise capacity in patients with hypertrophic cardiomyopathy and they suggest that, as in patients with chronic cardiac failure, other mechanisms should be considered.