The aim of this investigation was to study the effects of microtubule-specific drugs, taxol and colcemid, on the distribution of cell-associated extracellular matrix in dense cultures of fibroblasts. Immunomorphological examination of human seven-day cultures revealed a dense network of fibronectin and tenascin matrix filaments preferentially oriented in parallel with the long axes of cell bodies. Depolymerization of the microtubular system by colcemid and its disorganization by taxol led to rapid and drastic changes in the organization of matrix network: fibronectin and tenascin filaments became disordered and, in particular, lost any orientation. These data show that the microtubular system controls the morphological organization, not only of intracellular cytoskeletal systems, but also of extracellular matrix structures.