Antibiotic concentrations in pulmonary tissue samples and plasma were studied in this open investigation. Twenty-nine patients scheduled for elective pulmonary surgery received a single oral dose of 500 mg azithromycin 24, 72, 96 or 120 h prior to the operation; two patients received 250 mg b.i.d. Blood samples were taken before and at the time of resection, and tissue was obtained during surgery. Plasma and tissue concentrations of azithromycin were measured by high performance liquid chromatography (HPLC) and a microbiological bioassay. Only one patient had a detectable plasma concentration of azithromycin (0.13 micrograms/ml), measured 24 h post-dose by HPLC. However, high and sustained levels were found in lung tissue: mean concentrations measured by HPLC were 3.10 micrograms/g (SD +/- 2.17), 2.55 micrograms/g (SD +/- 1.36), 3.94 micrograms/g (SD +/- 2.40) and 3.13 micrograms/g (SD +/- 0.50) at 24, 72, 96 and 120 h, respectively. Bioassay results were similar to those for the HPLC assay. In summary, azithromycin levels in pulmonary tissue remained close to 3 micrograms/g for up to 5 days after a single oral 500 mg dose, in contrast to plasma levels which were much lower. The lung concentrations found are inhibitory for many sensitive respiratory pathogens and short-course azithromycin therapy is therefore a possibility.