Plasma and skin blister fluid concentration-time curves following a single oral dose of trimethoprim have been evaluated. Skin blisters were produced by the cantharides technique, using patches with cantharidin ointment. Trimethoprim concentrations in plasma following multiple doses of 200 mg were also determined. The maximal concentration in plasma after a single oral dose of 400 mg trimethoprim was 3.95 +/- 1.08 mg/l, and it was observed after 2 h, whereas in skin blister fluid the level was 2.21 +/- 0.62 mg/l, and it was delayed for up to 6 h. This means that a certain time is required for drug transfer from the capillaries via the basal membrane into blister fluid. Penetration of the drug into blister fluid, defined as the ratio of the areas under the trimethoprim level time curve in skin blister fluid to that of plasma, was 0.826 +/- 0.096. The steady-state concentration of trimethoprim in plasma during routine treatment with 200-mg doses ranged between 2 and 3.5 mg/l.