We studied the pharmacokinetic parameters of four fluoroquinolones—ofloxacin, ciprofloxacin, temafloxacin and sparfloxacin—in a mouse model of Streptococcus pneumoniae-inftcted lung. After a single subcutaneous injection, bioactivities were determined concomitantly in non-infected and infected animals, at a time at which pneumonia was well developed. Fluoroquinolones exhibited generally good activity at the site of infection. Infection did not affect the tissue distribution of either drug. However, the differences observed in non-infected controls (greater AUCs and longer half-lives of temafloxacin and sparfloxacin in lung and serum) were accentuated in infected mice, with probable trapping of temafloxacin and sparfloxacin at the site of infection and more persistent activity in the lung. These data suggest that the anti-pneumococcal activity of temafloxacin, and to a lesser extent sparfioxacin, were greatly favoured by their pharmacokinetic bchaviour in the infected lung.