A topical delivery system has been developed using 50% Transcutol (diethylene glycol monoethyl ether) to decrease the body burden of topically administered dexamethasone and hydrocortisone. The delivery system was evaluated in-vitro using a dissolution apparatus to measure the release of steroid from the gel. In 10 h, 29.6 +/- 0.39% dexamethasone and 45.5 +/- 0.84% hydrocortisone was released from the formulation compared with 23.0 +/- 0.48 and 39.9 +/- 0.77%, respectively, from control formulations without Transcutol. Ex-vivo evaluation was made using rat whole skin in a diffusion cell; the amount of steroid reaching the acceptor cell was significantly less from the formulation containing Transcutol compared with controls. There was also a 2-fold increase in the retention of dexamethasone and a 3-fold increase in the retention of hydrocortisone in the skin at the end of the permeation experiments compared with control experiments. In-vivo studies were made using a formulation containing [3H]hydrocortisone applied to rat skin, followed by measurement of total radioactivity in the blood. For the Transcutol formulation the area under the blood concentration-time curve (0-96 h) was 6.06 +/- 1.27 compared with 2.52 +/- 0.43 x 10(6) d min-1 mL-1 h for the control formulation, indicating a 58% reduction in body burden.