We show that a physiological role of the extensively studied cisternal Golgi rab protein, rab6, is modulation of Golgi apparatus response to stress. Taking exposure of cells to hypotonic media as the best-known example of mammalian Golgi stress response, we found that hypotonic-induced tubule extension from the Golgi apparatus was sensitive to GDP-rab6a expression. Similarly, we found that Golgi tubulation induced by brefeldin A, a known microtubule-dependent process, was inhibited by GDP-restricted rab6a, rab6a', and rab33b, the most commonly studied cisternal rab proteins. These GDP-rab levels were sufficient to inhibit rab-induced redistribution of Golgi glycosyltransferases into the endoplasmic reticulum (ER), also a microtubule-dependent process, and to depress Golgi membrane association of the GTP-conformer of rab6. Nocodazole-induced Golgi scattering, a microtubule-independent process, also was inhibited by GDP-rab6a expression. In comparison, we found similar GDP-rab expression levels had little inhibitory effect on another microtubule-independent process, constitutive recycling of Golgi resident proteins to the ER. We conclude that Golgi cisternal rabs, and in particular rab6a, are regulators of the Golgi response to stress and presumably the molecular targets of stress-activated signaling pathway(s). Moreover, we conclude that rab6a can regulate select microtubule-independent processes as well as microtubule-dependent processes.