Regulation of cholecystokinin (CCK) expression was studied in the human neuroepithelioma cell line SK-N-MCIXC. The cells were treated with the phosphodiesterase inhibitor isobutyl-methylxanthine and the tumor promoting phorbol ester, phorbol-12-myristate 13-acetate; activators of the cyclic AMP (cAMP) and protein kinase C (PKC) second messenger pathways, respectively. Levels of CCK mRNA were determined after 6, 12 and 24 hour drug treatments, with Northern blot analysis using human CCK cDNA hybridization probes. Activation of both cAMP and PKC second messenger pathways increased CCK mRNA levels in SK-N-MCIXC cells. These results indicate that the levels of CCK mRNA in SK-N-MCIXC cells are regulated by cAMP and PKC dependent mechanisms.