SUMMARY1. Cyclic AMP and cyclic GMP levels were determined in bovine splenic nerve segments in the absence and presence of (±) ‐ isoprenaline, (‐)‐phenylephrine, clonidine and ICI 63 197 (a phosphodiesterase inhibitor). The chosen concentrations of adrenoceptor agonists were those which are known to affect stimulation‐induced overflow of noradrenaline from nerve terminals.2. The mean levels of cyclic AMP ranged from 229 to 555 pmol/g of microwave irradiated tissue. Mean cyclic GMP levels ranged from 27.9 to 42.2 pmol/g.3.Isoprenaline enhanced cyclic AMP levels but did not affect cyclic GMP levels. The effect was blocked with (±)‐propranolol. ICI 63 197 increased cyclic AMP levels but did not change cyclic GMP. Phenylephrine and clonidine caused no consistent changes in cyclic AMP or cyclic GMP levels or in the concentration ratio between these two nucleotides.4.The results support the involvement of cyclic AMP in the enhancing effect of β‐adrenoceptor agonists and phosphodiesterase inhibitors on stimulation‐induced release of noradrenaline from sy