CHO cells express both of the phosphoinositidase C-linked G-proteins G q and G 1 1 G 1 1 α is some 2.5-fold more highly expressed than G q α in membranes of these cells. Following transfection and stable expression of CHO cells with DNA encoding the human muscarinic M1 acetylcholine (HM1) receptor, chronic treatment of the cells with the cholinergic agonist carbachol resulted in down-regulation of membrane levels of both G q α and G 1 1 α . Dose-response curves to carbachol produced identical EC 5 0 values for agonist-induced down-regulation of the two G-proteins and both were down-regulated with the same time course. These data indicate that the HM1 receptor interacts with and activates both G q α and G 1 1 α equivalently and non-selectively in a whole cell system in which the receptor has access to both G-proteins.