Studies were conducted to explore the effects of colchicine on the secretion and metabolism of retinol-binding protein (RBP) by the liver. In the vitamin A-deficient rat, the rate of secretion of RBP from the liver into the serum is greatly reduced, and RBP accumulates in the liver. Injection of retinol (dispersed in a 20% Tween 40 solution) into deficient rats stimulated a rapid secretion of RBP from the liver into the serum. Colchicine treatment markedly inhibited the retinol-stimulated secretion of RBP from the liver into the serum. The effect of colchicine was most pronounced during the early period after retinol injection, particularly during the first 30 to 60 minutes. Ninety minutes after retinol injection, the serum RBP level of colchicine treated rats was only 36% as great as that of the control rats. In parallel experiments, a quantitatively similar inhibition of very low density lipoprotein (VLDL) secretion by colchicine was observed in the retinol-deficient rats. In contrast, colchicine did not affect the overall rate of hepatic protein synthesis, as estimated from the incorporation of [(3)H]leucine into total liver and serum protein; the secretion of newly synthesized protein was, however, inhibited. When rats were treated with colchicine and then injected with retinol, the level of RBP in a Golgi-rich fraction obtained from the liver homogenate increased markedly as compared to the level of prealbumin. The inhibition of RBP secretion by colchicine suggests that the microtubules play a role in RBP secretion. By analogy to studies on VLDL and albumin, these data provide presumptive evidence that the Golgi apparatus and secretory vesicles are involved in RBP secretion.-Smith, J. E., D. D. Deen, Jr., D. Sklan, and D. S. Goodman. Colchicine inhibition of retinol-binding protein secretion by rat liver.