Non-overlapping applications of l-isoproterenol, a beta-adrenergic agonist, and the neuropeptide cholecystokinin 8-S produce long-lasting potentiation of evoked action potentials in the dentate gyrus. There is no corresponding modification of excitatory post-synaptic potentials. This effect, referred to as interactive long-lasting potentiation, is pharmacologically similar to the long-lasting potentiation produced by discontinuous or non-overlapping applications of l-isoproterenol. Metoprolol or propranolol, both beta-adrenergic antagonists, prevent interactive long-lasting potentiation, but D-amino-5-phosphonopentanoic acid, an N-methyl-D-aspartate receptor antagonist, does not. Cholecystokinin 8-S and beta-adrenergic receptors may activate a common intermediate in the interactive paradigm.