The concentrations of clarithromycin and its active principal metabolite, 14-(R)-hydroxy-clarithromycin, were determined in lung tissue obtained during lung resection and compared with concomitant concentrations in plasma. Concentrations of the parent and metabolite were determined by high-performance liquid chromatography. The 15 patients studied were given 500 mg orally every 12 h for a minimum of five doses to achieve steady-state concentrations. The mean concentrations of clarithromycin and 14-(R)-hydroxy-clarithromycin in plasma just prior to the final dose were 1.38 and 0.67 micrograms/ml, respectively, and those 4 h after the final dose (at the time of lung resection) were 1.89 and 0.80 microgram/mL, respectively. The concentrations of the parent and metabolite in lung tissue at the time of lung resection averaged 54.3 and 5.12 micrograms/g, respectively, with a mean calculated ratio of concentrations of the parent to metabolite being 11.3 in lung tissue and 2.4 in plasma. Clarithromycin and its active metabolite are extensively distributed into human lung tissue.