We investigated the effect of acute myocardial infarction (MI) on the hepatic clearance of theophylline in rats using the coronary artery ligation model. After 48 hr of ligation, there were significant changes in left ventricular performance in the MI rats, compared with controls, as indicated by elevated left ventricular end-diastolic pressure, reduced mean arterial pressure, and reduced left ventricular systolic pressure (20 +/- 2 vs. 12 +/- 3 mm Hg, p < 0.01; 90 +/- 6 vs. 101 +/- 6 mm Hg, p < 0.01; and 100 +/- 8 vs. 114 +/- 8 mm Hg, p < 0.01, respectively). Despite these changes, MI rats were able to maintain their cardiac output at rest (77.9 +/- 6.8 vs. 77.2 +/- 9.2 ml/min), and there was no change in mean central venous pressure (3 +/- 1 vs. 2 +/- 1 mm Hg). Although hepatic perfusion and oxygenation were preserved (17.3 +/- 2.2 vs. 18.7 +/- 3.3 ml/min and 127 +/- 27 vs. 125 +/- 19 mumol/min respectively), clearance of theophylline was reduced by 23% in the MI rats, compared with controls (0.86 +/- 0.20 vs. 1.12 +/- 0.17 ml/min, p = 0.01). There was no significant correlation between theophylline clearance and the infarct size (r = -0.038, p > 0.05). These findings demonstrate that the elimination of theophylline is impaired after acute MI, independent of any changes in hepatic perfusion or oxygenation.