To determine the effects of disopyramide on resting systolic left ventricular (LV) function and LV functional reserve, gated equilibrium radionuclide cineangiography was performed at rest and during maximal symptom-limited supine bicycle exercise in 12 patients after a single 300 mg oral loading dose of disopyramide, and in 22 patients (including the 12 patients just mentioned) after they received disopyramide 150 mg 4 times daily for 5 to 10 days (average 7). The oral loading dose (average serum level 3.6 +/- 1.3 micrograms/ml [standard deviation] produced decreases in ejection fraction in 9 of 12 patients with a decrease in average resting ejection fraction from 40 +/- 15% to 33 +/- 11% (p less than 0.005). However, the lower, sustained dosage of disopyramide was associated with a lower average serum level of 2.5 +/- 0.8 micrograms/ml and with smaller but significant decreases in ejection fraction in 3 of 22 patients during exercise only. At this dosage there was no significant decrease in average ejection fraction for the group at rest or during exercise. Adverse effects of disopyramide on ejection fraction occurred even in patients with previously normal LV function at rest. Hence, disopyramide may be associated with significant decreases in LV systolic function, particularly when given in high, oral "loading" doses. However, sustained therapy with lower dosages as well as lower drug levels is also associated with less depression of LV function.