Azithromycin is an azalide antibiotic with excellent in vitro activity against a wide variety of oral bacteria. It has a long half-life, good tissue penetration and is preferentially taken up by phagocytes. We investigated the microbiological efficacy of azithromycin as an adjunct to the non-surgical treatment of adult chronic periodontitis; its clinical efficacy is dealt with in a separate paper. 46 patients were treated in a double-blind placebo controlled trial. Microbiological assessment of the same periodontal pocket (initially > 6 mm) was made at weeks 0, 2, 3, 6, 10 and 22. Either azithromycin 500 mg 1 x daily for 3 days or placebo was given at week 2. Particular attention was paid to the numbers of black pigmented anaerobes and spirochaetes present since these are the most commonly implicated pathogens in periodontal disease. Pigmented anaerobes were significantly reduced at weeks 3 and 6 in patients who received azithromycin compared to placebo and remained lower, although not significantly so, throughout the study. Counts of spirochaetes were significantly reduced throughout the study in patients who received azithromycin compared to placebo. Our microbiological study suggests that azithromycin may be useful as an adjunct in the treatment of periodontal disease.