We have studied the effects of colchicine, an inhibitor of microtubular function, and cytochalasin B (CB), an inhibitor of microfilaments, on the uptake and degradation of asialo-glycoproteins in isolated rat hepatocytes. CB inhibited degradation only, while colchicine inhibited uptake as well as degradation. When the two were combined, no additive effect on degradation was found. The inhibition of uptake by colchicine could be accounted for by a reduction in the binding capacity of the plasma membrane for asialo-glycoprotein. The intracellular distribution of endocytosed asialo-glycoprotein was examined by isopycnic centrifugation in sucrose gradients. The results suggest that in cells treated with colchicine or CB, access of the endocytosed protein to the lysosomes is impeded. © 1979.