The mechanism of topically applied methyl nicotinate-induced local cutaneous erythema was studied in normal human subjects. Aqueous methyl nicotinate (0, 0.1, 1.0, 10.0, and 100 mmol/L) was applied to the volar forearms in quadruplicate after oral pretreatments with 25 mg doxepin hydrochloride, 600 mg ibuprofen, 50 mg indomethacin, 975 mg aspirin, and lactose placebo. The cutaneous vascular response was monitored by laser Doppler velocimetry. Although doxepin did not affect the cutaneous vascular response to methyl nicotinate, indomethacin, ibuprofen, and aspirin significantly suppressed the response. Because indomethacin, ibuprofen, and aspirin have different chemical structures, the common property of inhibition of the response to methyl nicotinate may be assigned to their common pharmacologic action, i.e., inhibition of prostaglandin bioformation.