1. The effect of drugs on the adenosine 3':5'-cyclic monophosphate (cyclic AMP) content of desmethylimipramine (DMI)-treated bullfrog paravertebral sympathetic ganglia was studied by radioimmunoassay. The adrenaline-induced hyperpolarization (Adh) in the tissue was recorded by means of the sucrose-gap technique. 2. In the presence of propranolol (1 microM) and DMI (0.5 microM), adrenaline (1 microM) significantly reduced the concentration of cyclic AMP in forskolin-treated ganglia. This effect was prevented by pertussis toxin (5 micrograms ml-1). 3. The relative potency for drugs which increased ganglionic cyclic AMP content was: 50 microM forskolin much greater than 5 mM fluoride greater than 2 mM fluoride greater than 2 mM isobutylmethylxanthine (IBMX) greater than 5 mM caffeine. In contrast, their relative potency for inhibition of the Adh was: 2 mM IBMX greater than 5 mM fluoride greater than 5 mM caffeine much greater than 2 mM fluoride greater than 50 microM forskolin. The Adh was unaffected by pertussis toxin (5 micrograms ml-1). 4. Although the Adh was slightly reduced by the extracellular application of 8-bromo (8-Br) cyclic AMP, the majority of the data suggest that the transduction mechanism underlying the Adh is independent of the intracellular cyclic AMP concentration and provide an example of an alpha 2-adrenoceptor-mediated response that occurs independently of inhibition of adenylate cyclase.