To explore whether the reported xanthoma-reducing effects of probucol are related to tissue-specific mechanisms of the drug, the influence of probucol on cholesterol efflux from cultured human skin fibroblasts was investigated. Incubation of cells with probucol led to a 2-fold enhancement of high-density lipoprotein-mediated cholesterol efflux. This result raises the possibility that probucol may reduce cholesterol accumulation in tissues through a cholesterol-mobilizing action.