The criteria to determine whether cyclic adenosine 3':5'-monophosphate (cyclic AMP) is or is not involved in a particular hormone response require to look for positive qualitive, quantitative and temporal correlations between the effects of the hormone on cyclic AMP levels and the physiological response. These requirements have been shown to be fulfilled in histamine and pentagastrin-stimulated gastric acid secretion of the frog (Necturus maculosus) and the rat. In dog and man, however, the available evidence does not support a role for cyclic AMP in the gastric secretory process; it remains a challenge for future research whether in those species cyclic guanosine 3':5'-monophosphate acts as an intracellular substitute for cyclic AMP.