Thirty patients with endocarditis caused by penicillin-susceptible streptococci were enrolled in one of two groups in this study. Fifteen patients received ceftriaxone (2 g once daily) for 4 weeks; the other 15 received the same dosage of ceftriaxone for 2 weeks and then received oral amoxicillin (1 g four times a day) for 2 weeks. For the 27 patients treated predominantly as outpatients, 380 days of hospitalization were avoided. Clinical cure was achieved for all patients in both groups. We conclude that ceftriaxone, alone or followed by a course of amoxicillin, is an efficacious mode of treatment for infective endocarditis caused by penicillin-susceptible streptococci. Treatment with these agents can be administered predominantly on an outpatient basis.