The antitumor drug paclitaxel (PTX) inhibits cell growth by binding to microtubules, the eukaryotic structures consisting of α- and β-tubulin. PTX also promotes the assembly of tubulin in the absence of microtubule-associated proteins. Although recent studies have implicated β-tubulin as the site of PTX binding, no information is available that relates α-tubulin to the binding site. In an effort to understand whether the α-tubulin is involved in the drug binding, we have studied the assembly of α-tubulin isoforms in the presence of PTX. The assembly results in the presence of 10 μM paclitaxel (PTX) show that the isoforms assemble at differential rates. The rate of assembly for tyrosinated Mα1/2 is about three-fold higher than that of the nontyrosinated Mα1/2 isoform. Such a strikingly different assembly behavior of the α-tubulin isoforms indicates that α-tubulin may be involved in the interaction of PTX with microtubules.