The efficacy and safety of a 4-week course of intravenous teicoplanin (500 mg every 12 h for the first 2 days and 10 mg/kg of body weight every 24 h thereafter) in the treatment of streptococcal native valve endocarditis in 20 patients were evaluated. All blood isolates were inhibited by a concentration of 0.12 micrograms of teicoplanin per ml. Serum bactericidal activity levels were measured 1/2 and 24 h after antibiotic infusion on days 5 to 7 of therapy in 19 patients, and titers of greater than or equal to 1:32 and greater than or equal to 1:8, respectively, were obtained with 17 patients (89%). On the other hand, for two patients who were infected with teicoplanin-tolerant Streptococcus bovis, serum bactericidal activity levels of less than 1:2 were found. Of 20 patients, 4 were excluded from further analysis because of protocol violation or prosthetic valve infection. Of the remaining 16 patients, 6 did not complete teicoplanin therapy because of early death (1 patient) or drug fever (5 patients). Among patients who developed drug fever, three who discontinued teicoplanin by day 15 were switched to penicillin therapy, whereas the remaining two, who discontinued teicoplanin on day 22 and 25, respectively, did not receive any further therapy and have shown no relapse during the follow-up. Of 10 patients who completed trial therapy, 9 were cured and 1 relapsed. It is concluded that a 4-week course of high-dose teicoplanin may be a useful regimen for home treatment of selected cases of streptococcal native valve endocarditis. However, drug fever and infection with teicoplanin-tolerant S. bovis may be factors of concern with this therapeutic approach.