The effect of duration of orally administered penicillin V potassium on the bacteriologic and clinical cure of group A streptococcal pharyngitis was evaluated. One hundred ninety-one middle-class patients received either seven days (96 patients) or ten days (95 patients) of therapy. Compliance with taking penicillin was assessed by multiple methods, including penicillinuria. Throat cultures were obtained during therapy and three times in the three weeks after therapy. M-precipitin and T-agglutinin typing were done on paired isolates of group A streptococci from patients who had recurrences. Patients treated for seven days had a significantly greater failure rate (30/96 [31%]) compared with patients receiving ten days of penicillin (17/95 [18%]). Compliance rates were high; 66% to 81% of patients showed penicillinuria throughout the study period. Treatment failure was not a function of poor compliance in either treatment group. The data support the current recommendation for ten full days of penicillin therapy and suggest that persistence of streptococci in the throat after adequate therapy may be common.