OBJECTIVE In vitro antibacterial activity of topical and systemic antihistaminic preparations containing different active substrates against the standard strains of two bacteria was evaluated. METHODS Four topical and 3 systemic preparations containing pheniramine maleate, chlorophenoxamine hydrochloride, and diphenhydramine hydrochloride were studied. The antibacterial activities of these preparations against strains of S. aureus (American Type Culture Collection, ATCC 29213) and S. epidermidis (ATCC 25212) were tested using the disc diffusion method. In addition, the Minimal Innhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) of parenteral preparations for these two bacteria were determined. RESULTS Pheniramine maleate-topical and pheniramine maleate-systemic had no activity against bacteria, but the others showed various rates of activity. Chlorophenoxamine hydrochloride-topical and chlorophenoxamine hydrochloride-systemic were the most effective (P < 0.05). Despite the same active substrate content, diphenhydramine hydrochloride-topical-1 and diphenhydramine hydrochloride-topical-2 yielded different results when they were compared with each other or with the other preparations. Diphenhydramine hydrochloride-topical-2 had a relatively higher rate of activity than diphenhydramine hydrochloride-topical-1. Inhibition zone diameters were 16.9+/-1.5 mm 12.3+/-0.5 mm for S .aureus, 17.4+/-1.0 mm 0 mm for S .epidermidis respectively (P < 0.05). MIC values of parenteral preparations were equal to or above 125 ?g/ml. CONCLUSIONS MIC values of parenteral preparations were higher than their blood levels in clinical use. Thus, effects of parenteral preparations may not have been reflected in routine clinical practice. However, topical forms have antibacterial activity due to additive substrates and the use of high concentration levels at the site of application. Therefore, in selection of topical forms for appropriate cases, these effects should also be taken into consideration. The antibacterial activity of topical antihistaminic preparations may be useful in certain dermatological pathology.