Recently, the transdermal route has received attention as a promising means to enhance the delivery of drug molecules, particularly peptides, across the skin. In this work, the skin penetration profiles of desmopressin acetate from a colloidal system (water-in-oil microemulsion) and an amphiphilic cream, a standard formulation, were determined using Franz diffusion cells and compared. In the case of the microemulsion, the total percentages of dose obtained from different skin layers(stratum corneum to subcutaneous tissue) were 3.30+/-0.67, 7.37+/-2.43 and 15.54+/-2.72 at 30, 100 and 300 min, respectively. Similarly, 5.19+/-0.96, 8.04+/-0.97 and 14.4+/-5.15% of the dose applied was extracted from the skin treated with the cream. About 6% of the applied dose reached the acceptor compartment from the microemulsion instead of 2% from the cream within 300 min. The concentration of drug that penetrated into the upper layers of the skin was higher from the cream than from the microemulsion at all time intervals. On the other hand, a higher amount of drug was found in the deeper skin layers and in the acceptor compartment from the microemulsion.