4-[(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)carbamoyl] benzoic acid (CAS 94497-51-5, Am-80) is a new synthetic retinoid which has been shown to have a potent topical antipsoriatic activity. Factors affecting the percutaneous absorption of Am-80 were studied with the intention of obtaining information for toxicity and clinical investigations. The percutaneous absorption of radioactivity was compared after topical application of 0.1% 14C-Am-80 ointment to female rats by simple application (SA), occlusive dressing technique (ODT), and application using lint (AUL). After single topical application to normal skin female rats, the percutaneous absorption of radioactivity was very low with no significant differences in the extent of absorption among the three application methods. In the stripped skin female rats, a distinct increase of the percutaneous absorption was observed indicating that it was markedly affected by the lack of the stratum corneum. Compared with the single dosing, a considerable increase of percutaneous absorption was observed following repetitive topical application once daily for 4 or 7 days to the normal skin female rats. The extent of increase was highest in ODT rats followed by SA rats, but was relatively low in AUL rats. The effects of concentration, dose and application area of 14C-Am-80 ointment on the percutaneous absorption of radioactivity were studied following topical application of 0.002%-0.008% 14C-Am-80 ointment to normal skin male rats by ODT to areas of 72 cm2/kg-360 cm2/kg (5%-25% of the body surface area) at ointment doses of 2g/kg-8 g/kg. When the application area and the amount of ointment applied were fixed at 144 cm2/kg (10% of the body surface area) and 2 g/kg, respectively, the amount of radioactivity absorbed increased in proportion to the 14C-Am-80 concentration in the ointment, whereas the rate of percutaneous absorption, expressed as the percent of dose, was nearly constant. When the 14C-Am-80 concentration in the ointment and the amount of ointment applied were fixed at 0.08% and 2 g/kg, respectively, both the amount of radioactivity absorbed and the rate of percutaneous absorption markedly increased with an increase in the application area. When the concentration of 14C-Am-80 in the ointment was set at 0.008% and the application area at 72 cm2/kg, 144 cm2/kg or 288 cm2/kg (5%, 10% or 20% of the body surface area), the amount of radioactivity absorbed increased as the amount of ointment applied increased for areas of the same, though the rate of percutaneous absorption remained almost constant. When the 14C-Am-80 concentration in the ointment was fixed at 0.008%, the amount of radioactivity absorbed increased markedly about 20-fold with 4-fold simultaneous increases in both the application area (from 72 cm2/kg to 288 cm2/kg) and the amount of ointment applied (from 2 g/kg to 8 g/kg).