Twenty-eight patients with acne were assigned to 4 weeks of treatment with OPC-7251 (a new fluoroquinolone derivative) 1% cream or the cream base in a double-blind manner to evaluate the antibacterial effect of the drug on resident bacteria in the hair follicles and to evaluate clinical response. Propionibacterium acnes was isolated from 21 of the 28 acne patients. When the number of P. acnes was compared before and after treatment, the posttreatment P. acnes count in the OPC-7251 1% cream group was significantly (p = 0.000) reduced compared with that in the cream base group. OPC-7251 1% cream was also significantly (p = 0.019) superior to the cream base in terms of clinical response. P. acnes and Staphylococcus epidermidis isolated from the acne lesions were selected for their susceptibility to various antibacterial agents. The minimal inhibitory concentration of OPC-7251 against P. acnes and S. epidermidis was 0.10 to 0.20 and 0.024 to 0.10 μg/ml, respectively, which indicates that the drug has a potent antibacterial effect.