Prepartum infusion of colchicine into mammary quarters of heifers inhibited normal development of bovine mammary secretory tissue. 2. In comparison with control, tissue from colchicine-infused quarters exhibited 22.6% less alveolar luminal area and 17.1% more interalveolar connective tissue area indicating a reduction in secretory activity. 3. Cytological analysis demonstrated that undifferentiated cells predominated in treated quarters whereas the majority of cells in control quarters were fully differentiated. 4. Although control quarters reached normal histological development by the third week postpartum, tissue from colchicine-infused quarters remained relatively immature. 5. Results suggest that (1) an intact microtubule system is necessary during the prepartum period if the mammary gland is to respond normally to lactogenic stimuli and (2) transient disruption of microtubule integrity during the prepartum period irreversibly suppresses differentiation of mammary epithelia during the subsequent lactation.