Azithromycin levels in tonsillar and/or adenoid tissue were determined in children (1.6-7.5 years old) who were scheduled for surgical removal of their tonsils and/or adenoids. The children received azithromycin oral suspension 10 mg/kg once daily for 3 days. Tissue samples were obtained during surgery 1 (n = 4), 2 (n = 5), 4 (n = 6), or 8 (n = 5) days after the last dose of azithromycin. Serum samples were also obtained from four children in each of these groups at the time of surgery. Mean tissue concentrations of azithromycin were 10.33 +/- 3.01, 7.21 +/- 4.04, 9.30 +/- 3.74 and 1.49 +/- 0.48 mg/kg, respectively, 1, 2, 4 and 8 days after the last dose. At the corresponding times, serum concentrations were markedly lower: 47.25 +/- 19. 19, 14.00 +/- 8.45, 8.00 +/- 2.16 and < 4 micrograms/L, respectively. The mean tissue:serum concentration ratios were, 227 +/- 54, 547 +/- 184 and 956 +/- 355, respectively, 1, 2 and 4 days after treatment. No adverse events attributable to azithromycin were observed in any of the 23 children who had received at least one dose of azithromycin. The study shows that levels of azithromycin in tonsillar and adenoid tissue were consistently higher than in serum and remained elevated up to 8 days after the end of dosing, supporting the use of a short-course (3-day), once-daily regimen of azithromycin in the treatment of upper respiratory tract infections.