This study was undertaken to determine whether continuous antirheumatic prophylaxis increased the risk of bacterial endocarditis (BE) or of its resistance to therapy. Sixteen episodes of BE occurred among children and adolescents with rheumatic heart disease who had been treated prophylactically for 3,615 patient years, a rate of 4.4 episodes per 1,000 patient years. This rate is similar to that observed in the preprophylactic era. The onset of BE in these patients often simulated a recurrence of rheumatic fever because of the frequent joint manifestations. Therefore, blood cultures are indicated whenever a patient with rheumatic heart disease has joint symptoms. Eight of the 16 organisms isolated were sensitive to penicillin in vitro; four were slightly sensitive; and four were resistant. The resistance was not of sufficient magnitude to interfere with a satisfactory therapeutic response. These data suggest no increased risk of BE in patients being treated prophylactically.