The tubulin protein is a major target of drug molecules, and consequently, tubulin inhibitors have attracted great attention as antimitotic antitumor agents for chemotherapeutic use. Stable microtubules (MTs) are known to contain acetylated alpha-tubulin. Acetylated tubulin is found in the dense networks and bundles of microtubules in the sensory and supporting cells. MTs containing acetylated alpha-tubulin in Ni2+-treated cells were resistant to disassembly induced by nocodazole, and at least partially resistant to cold temperature (0 degrees Celsius), which also depolymerizes MTs. Since acetylated alpha tubulin serves as a marker for the presence of stable MTs, the marked enhancement of alpha tubulin acetylation in Ni2+-treated cells indicates that stabilization of MTs may be an important mechanism by which Ni2+ induces cell injury since stabilized MTs in turn should favor MT bundling. The acetylated microtubules have been shown to be more drug resistant than nonacetylated microtubules. This increased stability is most likely due to the acetylation process.