An enhanced coupling of cholinergic muscarinic receptors to phosphoinositide metabolism had been previously observed in brain from immature rat. This study reports that the postnatal development of muscarinic receptor-stimulated phosphoinositide metabolism is also enhanced in cerebral cortex slices from immature Swiss-Webster and Balb-c mice, as compared to adults. Response to the agonist carbachol was lower on postnatal day 3, peaked between days 5 and 12 and then declined to adult levels. Density of muscarinic binding sites, measured with the M1 ligand [3H]telenzepine on postnatal day 7, was, on the other hand, only half of the adult value. Phosphoinositide hydrolysis stimulated by glutamate decreased with age, while that elicited by norepinephrine increased. These results are also similar to those previously reported in the rat. Ethanol has been found to inhibit muscarinic receptor-stimulated phosphoinositide metabolism in rat brain in an age-dependent manner. This was confirmed in mouse brain, where ethanol inhibited this response in cerebral cortex of immature but not adult animals. These results indicate that the enhanced muscarinic receptor-stimulated phosphoinositide metabolism, which coincides with the brain growth spurt, is similar in rats and mice. Mice may be a useful species in which to genetically manipulate muscarinic receptors to gain a better understanding of their potential role in brain development.