The diagnostic value of transesophageal echocardiography in monitoring the clinical course has been evaluated in 83 patients with echocardiographic evidence of infective endocarditis. A total of 103 vegetations attached to the aortic or mitral valves were detected by use of the transesophageal approach. The patients were monitored for a mean of 74 weeks and underwent a minimum of two consecutive transesophageal echocardiographic examinations. Group A included patients with increasing or remaining constant size of vegetation (8.2 +/- 1.5 to 11.2 mm, p less than 0.05) during 4 to 8 weeks of antimicrobial therapy, whereas group B was formed by patients with decreasing vegetation size (8.3 +/- 0.8 to 4.9 +/- 0.8 mm, p less than 0.05). The incidences of complications after diagnosis and onset of therapy was higher in group A than in group B: valve replacement (45% versus 2%, p less than 0.05), embolic events (45% versus 17%, p less than 0.05), perivalvular abscess formation (13% versus 2%, p less than 0.05), and mortality (10% versus 0%, respectively, p less than 0.05). Staphylococcus aureus was the most frequent organism isolated in group A (44% versus 11% in B, p less than 0.05) and Streptococcus viridans in group B (33% versus 18% in A, p less than 0.05). Blood cultures were negative in nearly 50% of the patients in each group. There was no difference in the incidences of complications in patients with positive or negative blood cultures. We conclude that an increase in vegetation size during antibiotic therapy predicts a prolonged healing phase of infective endocarditis. This prolonged healing period is associated with a significantly increased risk of complications, independent of blood culture results. Monitoring vegetation size contributes important information concerning prognosis and stage of risk, and it aids in the choice of patient management in infective endocarditis. Because embolic events after diagnosis and onset of treatment are less frequent in rapid-healing endocarditis, surgery cannot be recommended to prevent further events taking into account the high risk of surgery.