Background: The use of corticosteroids to treat periorbital dermatoses carries significant risk of serious side effects such as glaucoma, cataracts, and blindness. Studies to assess levels of corticosteroid penetration in the eyelid are lacking. Objective: We assessed corticosteroid penetration in eyelid skin in vitro to obtain information leading to the establishment of safer dosing regimens. Methods: Fluticasone propionate ointment, 0.005%, was applied (approximately 2-5 mg/cm²) to samples of human eyelid skin, and penetration was assessed by using modified Franz diffusion cells. Drug concentration was determined at 12, 24, 36, and 48 hours after application by liquid chromatography tandem mass spectrometry. Results: Only very small amounts of fluticasone propionate penetrated the skin (range, 0.618% ± 0.339% to 1.467% ± 0.695%). Conclusion: Further studies are warranted to examine the safety and efficacy of 0.005% fluticasone propionate ointment for the treatment of eyelid dermatoses. (J Am Acad Dermatol 2001;45:392-6.)