The aim of this study was to assess the rate and extent of transcutaneous delivery of prostaglandin E1 (PGE1) from various formulations [liposomal, novel biphasic, and nonliposomal (oil/water cream) delivery systems] in vitro using diffusion cells and in vivo using laser doppler flowmetry, to aid in the development of a topically active preparation for the treatment of male sexual dysfunction. Percutaneous absorption through adult human foreskin was tested in flow-through diffusion cells using [3H]PGE1. Nine healthy volunteers participated in the crossover, randomized, double-blind, placebo-controlled study, where 0.1 g of each preparation was applied to a 4 cm2 area on the forearm. Laserflo BPM2 blood perfusion monitor with Model P-430 skin probe was used for evaluating skin blood perfusion. Encapsulation of PGE1 into novel biphasic delivery systems resulted in significantly increased skin blood perfusion relative to traditional liposomal, nonliposomal, and placebo formulations (6.25 +/- 1.58 vs 2.72 +/- 0.79, 0.53 +/- 0.64, and 0.58 +/- 0.06 mLLD/min/100 g, respectively, n = 9). The in vitro absorption of PGE1 through foreskin correlated well with the in vivo data (respective permeability coefficients 3.33, 1.57, and 1. 40 x 10(-4) cm/h). Formulation parameters greatly influence the absorption of PGE1 through skin as measured by laser doppler flowmetry, but by the application of a novel topical delivery technology, a significant enhancement of PGE1 delivery can be achieved.