Stimulation of muscarinic cholinergic receptors in SK-N-SH human neuroblastoma cells resulted in a 1.5-4 fold increase in intracellular cAMP levels. This unusual response was sensitive to atropine and pirenzepine but insensitive to pertussis toxin. It was observable regardless of whether basal, PGE1- or forskolin-stimulated cAMP levels were measured. The half-maximal concentration for carbachol-stimulation of cAMP levels (6 microM) was similar to that for the previously determined carbachol-induced stimulation of phosphoinositide turnover in these cells, suggesting that the former is mediated by the latter. These data indicate that cross-talk between the phosphoinositide turnover system and the adenylate cyclase system results in increased cAMP levels in SK-N-SH cells in response to muscarinic receptor stimulation.