The aromatic synthetic retinoid acid derivative, acitretin, is efficacious in several cutaneous diseases. Its toxicological profile makes a topical form with no or reduced systemic adverse effects desirable. Direct application of a topical acitretin formulation might result in therapeutic skin concentrations at the site of the disease while minimizing systemic exposure. The present studies define the percutaneous absorption characteristics of acitretin from an isopropylmyristate formulation. We investigated, in-vitro, (1) the role of receptor solution variations, (2) the role of skin modifications, (3) the influence of skin from three different species on the absorption of topically applied acitretin and (4) the drug distribution within the skin. Addition of solubilizers (Polyethylenglycol-20 and albumin) to the receptor solutions improved the flux of acitretin through monkey skin, whereas the acitretin concentration in the skin was not affected by the various receptor solutions used. Acitretin flux through tape-stripped monkey skin and dermis was only slightly higher than through intact skin. Acitretin concentration in human skin was significantly higher than in rhesus monkey or guinea-pig skin. Topical application of acitretin can produce dermal concentrations in excess of those achieved by therapeutic oral doses.