The livers of control and griseofulvin-treated mice were perfused with a detergent solution to study the relationship of Mallory body formation to the hepatocyte microtubules and intermediate filaments using electron microscopy and morphometric analysis. Numerous microtubules and intermediate filaments were found throughout the cytoplasm of hepatocytes, especially around the nucleus and the cell border, in both the griseofulvin-treated mouse livers and controls. Intermediate filaments were numerous in the cytoplasm around Mallory bodies. Morphometric analysis revealed that griseofulvin feeding did not significantly alter the amount of microtubules and intermediate filaments in hepatocytes. There was no significant decrease in microtubules and intermediate filaments in Mallory body-containing hepatocytes. In griseofulvin-treated mice, typical Mallory bodies were observed as randomly oriented, relatively short, approximately 17-nm. thick filaments. After detergent extraction some Mallory bodies were observed to be composed of thinner (approximately 8.4 nm) filaments, which morphologically resembled intermediate filaments. Our results suggest that Mallory bodies are composed of intermediate filaments decorated with a nonfilamentous substance that can be extracted by the Triton X-100. The data do not support the theory that Mallory bodies form at the expense of intermediate filaments as has been suggested from immunofluorescence studies. Our results do not support the antimicrotubule hypothesis of Mallory body pathogenesis.