The diffusion of clarithromycin and roxithromycin into respiratory tract tissues was studied in 174 adult patients undergoing surgery. Patients received clarithromycin 250 mg orally (500 mg in the case of lung tissue), or roxithromycin 150 mg orally, both given every 12 h, for three days with the last dose administered at different times before surgery. Clarithromycin reached peak tissue levels 4 h after administration and achieved mean peak concentrations of 8.32 mg/kg±2.57 in nasal mucosa, 6.47 mg/kg±2.8 in tonsil, and 17.47 mg/kg±3.29 in lung tissue. Roxithromycin reached peak tissue levels between 4 and 6 h after administration, achieving mean peak concentrations of 1.78 mg/kg±0.73 in nasal mucosa, 2.2 mg/kg/l±1.21 in tonsil, and 2.14mg/kg±0.87 in lung tissue. Clarithromycin and roxithromycin demonstrated contrasting pharmacokinetic behaviour. Roxithromycin was characterized by high concentrations in serum and low concentrations in tissues. Clarithromycin on the other hand, is characterized by therapeutic serum concentrations and high tissue concentrations.