The choice of antimicrobial agents for treatment of prostatitis should be based on two factors: in vitro sensitivity of isolated pathogens and potential intraprostatic penetration of the molecule. Unfortunately, only a few antibiotic agents penetrate prostatic fluid which is the primary site of infection. Lomefloxacin, a once-daily difluoroquinolone, could play a central role in the therapy of prostatitis because it has sufficient liposolubility, low ionization (pKa), low protein binding, small molecular size, long serum elimination half-life and it can pass from interstital fluid across prostatic cells into the lumen. This study was carried out on 12 patients (mean age 65 years) with normal hepatic and renal function, divided into two groups of 6 subjects each. Lomefloxacin was administered for perioperative antisepsis at the dose of 400 mg orally once a day for 4 days. Serum and tissue were sampled in the two groups of patients 4 h (Group A) and 8 h (Group B) respectively after the last drug administration. Tissue penetration was higher than serum, with a T/S >2 in the prostatic capsule and seminal blister, and a T/S >1.6 in the adenomatous tissue, in both groups of patients. In addition, the prostatic tissue concentrations exceeded the MIC for the main pathogens usually involved in urogenital infections. Therefore, because of its pharmacokineitic and pharmacodynamic characteristics, lomefloxacin is proposed as an efficacious therapeutic option, even for the treatment of chronic prostatitis.