To determine whether the agonist-mediated endocytosis of muscarinic receptors and Gq/11 are mechanistically related events, the internalization of Gq/11 was monitored under conditions established to prevent muscarinic receptor endocytosis. Incubation of SH-SY5Y neuroblastoma cells with oxotremorine-M resulted in the translocation of both muscarinic receptors and Gq/11 into a 'light vesicle' membrane fraction. Although muscarinic receptor translocation was prevented by either the depletion of phosphoinositides or by disruption of clathrin assembly, the endocytosis of Gq/11 was unaffected. These results demonstrate that the agonist-induced internalization of muscarinic receptors and Gq/11 proceed via distinct mechanisms.