Paramount among issues relating to the transmissible spongiform encephalopathies (also known as prion diseases) is the absence of any effective therapy. This need has been heightened by the substantial European and emerging global problem of bovine spongiform encephalopathy and consequent variant Creutzfeldt-Jakob disease. Stimulated by the recent reports of a potent antiprion effect in cell culture-based clearance assays, we studied the utility of quinacrine in a well-characterized in vivo model of mouse-adapted transmissible spongiform encephalopathy. Our results failed to show any evidence that quinacrine is effective when using the simple but objective measure of survival prolongation.