Direct addition of C2-ceramide to DA neuroblastoma cells or primary DA neurons in vitro resulted in dose-dependent cytotoxicity, and pharmacological inhibition of SMases with three different inhibitors of SMase function to block ceramide generation during TNF exposure (but not inhibitors of de novo ceramide synthesis) afforded significant protection from TNF-induced cytotoxicity. The gene discussed is TNF; the disease is neuroblastoma.