The in vitro disassembly of microtubules from mammalian brain and Physarum is inhibited by various derivatives of taxol and baccatine III. Structure-activity relationships of the taxol derivatives were identical for both mammalian brain and Physarum microtubules. This observation suggests that the site of action of taxol has been preserved during the evolution of these two different eukaryotic lines. The substituent at C-13 of taxol was required to prevent disassembly of brain microtubules with or without microtubule-associated proteins. In contrast, both taxol and baccatine III prevented the disassembly of Physarum microtubules to the same extent, showing that the substituent at C-13 was not required in the interaction with Physarum tubulin. The different effects of baccatine III and taxol derivatives indicate that measuring the disassembly of microtubules from different organisms could be a useful parameter in the search for derivatives exhibiting antiparasitic activity.