Doxycycline is a synthetic tetracycline compound whose main advantages over tetracycline hydrochloride are increased oral absorption, prolonged serum half-life and decreased gastrointestinal side-effects. The purpose of this study was to measure the concentration of doxycycline in gingival fluid and blood after oral administration. 4 volunteers were given doses of 100 mg doxycycline every 12 h on the first day of antibiotic administration followed by a maintenance dose of 100 mg per day for an additional 4 days. 3 of these volunteers were also given tetracycline hydrochloride every 6 h for 5 days either 1 month before or after doxycycline administration to compare gingival fluid levels of these 2 tetracycline compounds. Gingival fluid was sampled from 4 gingival sites in each volunteer at hourly intervals from hours 0 to 6, 9, 24, 27, 48 to 54, 57, 72, 75, 96 to 102 and 105. Blood was sampled by finger puncture at hours 0, 3, 6, 24, 48, 54, 72, 96 and 102. Antibiotic levels in gingival fluid and blood were measured using an agar diffusion assay method. The results demonstrated that doxycycline achieved much higher levels in the gingival fluid than in blood and yielded comparable gingival fluid levels to those achieved by tetracycline hydrochloride. Doxycycline levels in gingival fluid ranged between 1.2 micrograms/ml and 8.1 micrograms/ml in the first 24 h and generally achieved 3-10 micrograms/ml after 48 h. Blood levels after 48 h ranged between 2.1 micrograms/ml and 2.9 micrograms/ml. Tetracycline hydrochloride in gingival fluid after 48 h was generally in the range of 4 micrograms/ml-10 micrograms/ml with blood levels between 2.2 micrograms/ml and 3.4 micrograms/ml.(ABSTRACT TRUNCATED AT 250 WORDS)