The effect of carbon tetrachloride (CCl4) and methylene chloride (MC) on the hepatic microtubular system and its relationship to the development of fatty liver were examined. Hepatic microtubule content was assessed using a specific colchicine-binding assay. These studies demonstrated that these 2 chlorinated methanes had no early effect on hepatic microtubule content. A significant decrease in microtubules was not observed until after the development of the fatty liver. In vitro tubulin polymerization studies demonstrated that neither CCl4 nor MC had a significant effect on lag-time before tubulin assembly, rate of assembly or the maximum amount of polymerization achieved. It is concluded that an impairment in hepatic microtubule assembly is not responsible for the development of the chlorinated alkane-induced fatty liver.