The effects of metoprolol on early infarct expansion after acute myocardial infarction were studied in rats (n = 54) that underwent either left coronary artery ligation (MI) or sham operation. Immediately after surgery, the rats received either metoprolol (M) by mouth, which had been dissolved in drinking water, for 72 hours supplemented with three intraperitoneal doses over the first 24 hours or no treatment (H2O). Three days after the initial surgery, hemodynamic measurements were made before and after volume loading. The rats were killed, the hearts were removed, and passive pressure-volume curves were obtained. The hearts were then fixed at a constant pressure and analyzed morphometrically. Infarct size was nonsignificantly lower in the metoprolol-treated group compared with the untreated group (38% +/- 5% MI-M vs 48% +/- 3% MI-H2O, p = 0.10) Compared with infarcted untreated rats, infarcted metoprolol-treated rats had a lower heart rate (322 +/- 13 beats/min MI-M vs 452 +/- 19 beats/min MI-H2O, p < 0.001), lower left ventricular systolic pressure (63 +/- 4 mm Hg MI-M vs 90 +/- 6 mm Hg MI-H2O, p = 0.004), and lower +dp/dt (1340 +/- 169 mm Hg/sec MI-M vs 2872 +/- 273 mm Hg/sec MI-H2O, p < 0.001), but left ventricular end-diastolic pressure and cardiac index did not differ between the two groups. Left ventricular weight corrected for body weight was higher in infarcted rats treated with metoprolol compared with infarcted untreated rats (2.76 +/- 0.07 gm/kg MI-M vs 2.41 +/- 0.09 gm/kg MI-H2O, p < 0.05). The initial slope of the pressure-volume relationship Ki, an index of operative volume stiffness, was lower in infarcted rats treated with metoprolol compared with infarcted untreated rats (p = 0.03). There were, however, no significant differences in the expansion index, thinning ratio, or left ventricular volume between the two infarcted groups. Thus metoprolol therapy begun in the immediate postinfarction period promotes an increase in left ventricular weight and reduces operative volume stiffness but has no significant effect on indexes of early infarct expansion.