Genetic evidence has been obtained indicating that the responsiveness of CHO cells to cAMP requires an intact cADepPK system. DNA carrying mutant RI and C subunit genes has been transferred to wild-type cells. Recipient cells carrying the DNA have been detected by selecting for expression of the phenotype for cAMP resistance. We are in the process of cloning a functional mutant RI subunit to use as a moveable genetic element that can confer cAMP resistance on recipient cells. This cloned gene should allow us to test hypotheses concerning the mechanism of cAMP regulation of transcription in mammalian cells.