BACKGROUND Propionibacterium acnes is the predominant organism in acne lesions, but the sensitivity of different biotypes of P. acnes to therapeutic agents has seldom been reported. METHODS To characterize biotypes of P. acnes and to measure the effects of Keigai-rengyo-to (KRT) and minocycline (MINO) on clinical P. acnes isolates. RESULTS Propionibacterium acnes biotype III (BIII) is the most common form of identified acne lesion, followed by P. acnes biotype I. BIII was isolated from mild, moderate and severe severity and the average lipase activity of BIII was higher than that of Biotypes I, II, IV and V. No significant differences in the decrease of free fatty acid production elicited by KRT or by MINO were found between BIII and the other biotypes. The degree of decreased butyric acid production was greater than that of propionic acid production in the medium supplemented with MINO. The percent decrease of butyric acid production elicited by 1 mg/mL of KRT was the same as that elicited by 0.1 microg/mL of MINO. Among biotypes of P. acnes, the minimal inhibitory concentrations of agents tested were generally higher in erythritol-positive biotypes than in erythritol-negative biotypes. CONCLUSION The high frequency of BIII might be responsible for the severity of acne in patients. It seems that if the same concentrations of MINO and KRT are used, the antilipase activity of MINO is stronger than that of KRT. Minocycline also has a direct anti-lipase activity against P. acnes. The mechanism underlying the influence of erythritol on the susceptibility of P. acnes to these agents remains unknown.