Thirty-four drug addicts with endocarditis were studied to evaluate the prognostic significance of vegetation size and its short-term changes, as determined by two-dimensional echocardiography. Among 43 episodes of endocarditis, vegetations were detected in 27 (63%), confined to the tricuspid valve in 20 patients, mitral valve in one, aortic valve in two, and both tricuspid and mitral valves in four. All vegetations were large (greater than or equal to 1 cm) (mean maximal dimension, 1.7 +/- 0.5 cm). Medical cure was achieved in all 16 patients without vegetations and in 18 (90%) of 20 patients with tricuspid valve vegetations. One patient with tricuspid vegetation and polymicrobial infection died of respiratory failure. Surgery was required for one patient with tricuspid vegetation, all three patients with isolated left-sided endocarditis, and two of four patients with multivalve involvement. Short-term changes of tricuspid valve vegetations during therapy (one to eight weeks) did not correlate with clinical outcome. Although large tricuspid vegetations may occasionally identify a subset at risk for complications, most patients with isolated tricuspid valve endocarditis have a benign prognosis.