Systemic absorption of metronidazole was studied after one application of a metronidazole 25% dental gel into inflamed periodontal pockets. 14 patients with periodontal disease participated. Metronidazole gel was applied into the pockets of all teeth with probing depth > or = 5 mm, minimum 10 teeth/patient. Excess gel was carefully collected in order to calculate the amount of metronidazole applied into the pockets. Blood samples for analysis of metronidazole in plasma were taken before and up to 72 h after application. To determine the bioavailability of metronidazole administered as gel, the patients were later given an i.v. dose of 100 mg metronidazole. Metronidazole was quantified by HPLC. The mean actual dose of metronidazole in gel was 55 mg (SD: 24 mg, range: 29-103 mg). Allowing for the fact that excess gel corresponding to about 60% of the applied amount of metronidazole under normal clinical conditions may be swallowed, the systemic load after one application of metronidazole 25% dental gel will still be less than after one metronidazole 250 mg tablet. Peak plasma concentrations varied between 223 and 1303 ng/ml (mean: 581 ng/mk, SD: 320 ng/ml) and were reached within 2 to 8 h (mean: 4.4 h). The mean bioavailability of metronidazole dental gel was 71%.