There are a number of potential sites of infection in the lower respiratory tract. This review summaries the nature of these sites and the ways in which antibiotic penetration can be studied. The results of a single-dose and a multiple-dose study of the penetration of sparfloxacin into the respiratory tract are also provided. After a single oral dose of sparfloxacin 400 mg or a 400 mg loading dose on day 1 followed by 200 mg daily for 2 days, sparfloxacin concentrations in the bronchial mucosa, epithelial lining fluid and alveolar macrophages were higher than the corresponding concentrations in serum. Compared with other fluoroquinolones, sparfloxacin achieves higher concentrations at these sites. Sparfloxacin diffusion into maxillary sinus mucosa has been studied in patients with chronic maxillary sinusitis undergoing surgery. High concentrations of sparfloxacin were detected in sinus mucosa 2 to 5 h after administration of a single dose of sparfloxacin 200 or 400 mg.