The effects of cyclic adenosine and cyclic guanosine nucleotides and theophylline upon gastrin synthesis and secretion were examined in rat antral mucosa maintained in organ culture. In concentration-response experiments, cyclic AMP, dibutyryl cyclic AMP and theophylline stimulated gastrin release and incorporation of [3H]-tryptophan into gastrin: a high degree of positive correlation was demonstrated between gastrin synthesis and gastrin release in response to control and test culture conditions. Cyclic GMP and dibutyryl cyclic GMP also stimulated gastrin secretion to a degree similar to that seen with cyclic AMP. These studies provide support for the proposal that the cyclic nucleotide system is involved in the stimulation of gastrin synthesis and release by the antral gastrin cell.