The time-dependent concentration curves of sulphadimethoxine in plasma and cantharidin-induced skin blister fluid have been evaluated following a single oral dose of 1 g. In contrast to other drugs, sulphadimethoxine exhibited two-stage penetration into the blister fluid, the second peak concentration being higher than the first. The maximum plasma concentration of 94.1 mg.l-1 was observed after 4 h, and in skin blister fluid the first peak of 25.6 mg.l-1 was found after 7 h, and the second of 58.0 mg.l-1 occurred after 30 h. The penetration of sulphadimethoxine into skin blister fluid, defined as the ratio of the AUC there to that in plasma was 0.748. The results suggest that sulphadimethoxine penetrates into skin blister fluid to a great extent from plasma and achieves concentrations exceeding the MIC for susceptible pathogens, but it requires a relatively long time to do so.