Three hundred six children with probable Group A beta-hemolytic streptococcal pharyngitis were enrolled in a randomized double blind trial to compare the effects of immediate vs. delayed treatment with oral penicillin V. Among the 229 culture-positive patients, 111 were randomly assigned to receive penicillin V immediately and 118 to receive a placebo for 48 to 52 hours followed by penicillin V. Patients were evaluated clinically for 48 to 52 hours following initiation of treatment. The Streptozyme test was used to measure acute to convalescent antibody titer. Both regimens resulted in a greater than 92% cure rate. Early treatment was associated with significantly fewer and milder signs and symptoms on Day 3 and a significantly lower rise in the antibody titer. On the other hand we found 8 (7%) relapses and 18 (16%) early and 14 (13%) late recurrences in this group; all were significantly higher than the corresponding numbers of 2 (2%), 6 (5%) and 4 (3%), respectively, in the late treatment group. This study shows the beneficial effect of early treatment with penicillin V on the clinical course of Group A beta-hemolytic streptococcal pharyngitis. This study also shows that delayed penicillin treatment may be associated with a lower incidence of subsequent Group A beta-hemolytic streptococcal pharyngitis.