This chapter describes a fixation method using tannic acid with glutaraldehyde for the study of microtubule structure and provides mechanism of the effect tannic acid. Various applications of the use of tannic acid to other ultrastructural studies are also discussed. Tannic acid is a natural product and a mixture of many types of polyphenolic compounds. Several mechanisms have been proposed to explain various effects of tannic acid observed in electron micrographs. Tannic acid acts as a fixative because it causes polypeptides with more than nine amino acids to precipitate, if the pH is optimally controlled. These polypeptides that precipitate with tannic acid are probably not covalently crosslinked because the precipitates can be resolubilized by altering pH or by removing tannic acid by dialysis. Covalent crosslinking may not occur in the biological specimen treated with tannic acid; tannic acid can stabilize certain biological structures, such as many types of membranes, interstitial structures, and isolated tubulin paracrystals induced by vinblastine.