Vinblastine has been used in vivo as well as in vitro to study the effects of antimicrotubular agents on the mechanisms of protein degradation. The administration of vinblastine (l-2mg/100g) in vivo has little or no effect on the endocytic uptake of intravenously injected14C-leucine-labeled microsomes and denatured125I-albumin by the rat Kupffer cells. By contrast the degradation of these substances is inhibited by approximately 40%. Vinblastine does not influence the uptake of125I-polyvinylpyrrolidonesilica particles (Percoll) by the liver, but it shifts the subcellular distribution of the radioactivity towards the microsomal fraction. The impaired degradation of endocytosed material following vinblastine treatment is not restored to control values by blocking the autophagic pathway. In contrast to the previously described stimulation of autophagic degradation [14-16] in vivo, vinblastine in vitro inhibits the proteolytic rate of isolated hepatocytes by approximately 25%. In Ehrlich’s ascites tumor cells the “accelerated” proteolysis induced by nutrient omission is decreased by 30 to 40% in the presence of vinblastine. No effects on “basal” proteolysis are seen in these cells.