The MTT assay was used to measure the effects of pamidronate, clodronate and mevastatin on the cell viability of Ewing's sarcoma cell lines 6647, CADO-ES-1, ES-2, ES-3, RD-ES, SK-ES-1, STA-ET-2.1 and VH-64. Treatment of these cells with pamidronate inhibited cell viability in a time- and dose-dependent manner. After a 72-h incubation period with 50 μM pamidronate, cell numbers were reduced by up to 80%, whereas the monophosphonate analog 3-aminopropyl phosphonate had no effect at concentrations up to 2 mM. Clodronate reduced cell viability by maximally 40% at 1 mM. These data provide the first evidence for a direct growth-inhibitory effect of pamidronate on Ewing's sarcoma cells. Hence, pamidronate definitely merits a more thorough exploration into its potential use in the therapy of patients with Ewing's sarcoma.