Abstract Effects of G proteins on the phosphorylation of muscarinic receptors (mAChRs) have been examined. Cerebral but not atrial mAChRs were phosphorylated by any one of three types of protein kinase C and 4–6 mol of phosphate were incorporated per mol of mAChR, mostly in the 12–14 kDa from the carboxyterminus. Atrial mAChRs were better substrates of cAMP-dependent protein kinase than cerebral mAChRs. Phosphorylation of mAChRs by protein kinase C or cAMP-dependent protein kinase was not dependent on the presence of agonists and G proteins except that a slight inhibition by G proteins was observed probably because G proteins were also substrates of the two kinases. Agonist-dependent phosphorylation of atrial mAChRs or recombinant human mAChRs (m2 subtype) by a kinase (mAChR kinase), which is the same or very similar to β adrenergic receptor kinase (βARK), was found to be regulated by the G proteins in a dual manner; stimulation by G protein βγ subunits and inhibition by G protein αβγ trimer. The inhibition by the G protein trimer is restored by addition of guanine nucleotides and is considered to be due to the formation of a ternary complex of agonist, mAChR and guanine nucleotide free G proteins. The stimulation by G protein βγ subunits was also observed for the light- or agonist-dependent phosphorylation of rhodopsin and βAR by the mAChR kinase but not for the light-dependent phosphorylation of rhodopsin by rhodopsin kinase. The phosphorylation by βARK 1 was also found to be stimulated by G protein βγ subunits. The βγ subunit is considered to interact with the extra 130 amino acid residue carboxyterminal tail of βARK, which does not exist in rhodopsin kinase, and the interaction results in the activation of the kinase. We may assume that the G protein coupled receptor kinase is an effector of G protein βγ subunits and that one of the functions of βγ subunits is to stimulate the phosphorylation of G protein coupled receptors thereby facilitating their desensitization.