BACKGROUND: Sclerosants are used to treat vascular malformations. Owing to variations in the flow, the injected concentrations and the duration of exposure of these sclerosants are altered. Therefore, the clinical effectiveness of sclerotherapy is variable. OBJECTIVE: The objective was to evaluate the differences in clinical response, usually observed among ethanol, polidocanol, and OK-432, using an in vitro sclerotherapy model. METHODS: Endothelial cells were cultured and exposed to different concentrations of the sclerosants for 5 seconds and the remaining viable cells were counted using a MTT assay kit. Dyes were used to visualize the morphologic changes. Precipitant formation in blood was also evaluated. Finally, the degree of ICAM-1 expression, after exposure to lower concentrations of these sclerosants, was studied using immunocytochemistry. RESULTS: Only ethanol causes precipitant formation and kills almost all cells from 30% concentration. Polidocanol begins to disrupt the cell membrane from 0.0125% onward. Only OK-432 induces ICAM-1 expression. CONCLUSION: Ethanol's strong precipitant-forming effect may induce thromboembolism, thus enhancing sclerosis. Polidocanol's endothelial cell-lysing effect was clearly documented. OK-432 may mediate its effect by inducing inflammatory response of the endothelium via ICAM-1 expression. This in vitro model may be useful in evaluating other sclerosants as well.