In an attemptto prevent postoperative sequellae dentists often prescribe penicillin or other antibiotics following periodontal surgery. A review of the literature shows conflicting reports about this procedure. This study investigated the efficacy of prophylactic penicillin in 19 human subjects undergoing periodontal surgery. Following initial therapy, flap surgery was undertaken in at least two comparable quadrants in each patient. Using a split mouth technique, patients were either given phenoxymethyl penicillin or a placebo following flap surgery for 5 days. Pain, infection, plaque levels, gingivitis and crevicular fluid flow were measured during a 4 week period. There were no differences between the placebo or penicillin sides in any of the parameters studied, except that the pain experience was significantly lower on the penicillin operated side. Within the limitations of this study it is difficult to substantiate the routine use of antibiotics following periodontal surgery.