The protein kinase C activator phorbol 12-myristate 13-acetate (PMA) induces rapid and reversible shape changes in cultured fibroblasts: extension of motile lamellas is followed by transformation of these lamellas into nonmotile stalklike processes. This "lamella-to-stalk" transformation was found to be associated with the formation of microtubules enriched in detyrosinated alpha-tubulin. This change was local: microtubules in motile lamellas at the distal ends of the processes and in the cell bodies were not enriched in detyrosinated alpha-tubulin. Detyrosinated microtubules in the processes were more resistant to Colcemid treatment than other microtubules of PMA-treated and control cells. The effects of PMA were reversible and could be abolished by sphingosine, a specific inhibitor of protein kinase C. Besides modification of microtubules, lamella-to-stalk transformation is associated with the ingrowth of intermediate filaments into the extensions. Earlier it was found that this transformation is also associated with the profound reorganization of the system of actin microfilaments. Thus, all three cytoskeletal systems are altered simultaneously during PMA-induced formation of processes. Similar "cytoskeletal synergies" may play essential roles in many morphogenetic processes--e.g., in the growth of neurites.