Complete resolution of major pulmonary embolism (PE) treated with heparin alone can often take > 3 weeks. Thrombolytic agents effectively resolve pulmonary artery thrombi within a few hours. However, the effect of the 2 types of treatment on recovery of right ventricular function has not yet been followed for periods of > 24 hours. We prospectively examined 40 consecutive patients with documented major PE (symptoms being present for < or = 8 weeks). After diagnosis, 27 patients (68%) were treated with alteplase plus heparin and 13 (32%) with heparin alone. There was no significant difference between the 2 groups with regard to baseline parameters. At 12 hours, systolic pulmonary artery pressure decreased from 56 +/- 20 to 37 +/- 21 mm Hg in the alteplase group, and from 50 +/- 11 to 46 +/- 12 mm Hg in the heparin group (significantly more; p = 0.016). On echocardiographic follow-up, a decrease in end-diastolic dimensions of the right ventricle and an increase in left ventricular dimensions was significantly more pronounced in the alteplase group (p <0.001 and p = 0.05, respectively). The incidence of right ventricular dilation and paradoxical septal wall motion decreased significantly only in the thrombolyis group. However, at 1-week follow-up, no difference was seen between the 2 groups regarding the overall change in right or left ventricular dimensions or the final values of other echocardiographic parameters. Thus, echocardiography is particularly useful for hemodynamic follow-up of major PE. Thrombolysis may rapidly reduce pulmonary artery pressure, but resolution of right ventricular pressure overload also occurs within 1 week in patients treated with heparin alone.