Ganglionic cyclic AMP and cyclic GMP are increased by raising [K+In (Roch and Kalix, 1975;Kalix, 1976). Intact preganglionic nerves and Ca2+ are required for the K+-induced increase of cyclic AMP, conditions that suggest transmitter activation of adenylate cyclase (Roch and Kalix, 1975). Less is known about the K+-induced increase in ganglionic cyclic GMP.Kalix (1976) found a two-to threefold increase in cyclic GMP in bovine sympathetic ganglia incubated in solutions containing 100 mM-K+. The role of CaZt and nerve terminals in the response to K+ was not studied. It is of interest, however, that K+-induced increase of cyclic GMP in brain slices occurs by a Caz+-dependent process (Ferrendelli et a]., 1973; Ferrendelli, 1978). Since it is not possible to eliminate nerve terminals in brain slices, their role in guanylate cyclase activation by K+ cannot be studied directly. Because blocking drugs for transmitters are without effect on the response to K+, Ferrendelli (1978) suggests that depolarization per se causes the increase in neuronal cGMP.Elevated K' causes a 40-to 50-fold increase in cGMP (vide infro) in rat superior cervical ganglia, thus providing the opportunity to study the role of Caz+ and preganglionic terminals when guanylate cyclase activity is increased by K+. The nerve terminals can be removed easily by surgical procedures. A comparison is made with guanylate cyclase stimulation by sodium azide (Murad et al., 1978).Superior cervical ganglia are removed from male Sprague-Dawley rats, desheathed, and equilibrated for 30 min in Locke's solution containing 136 m~-N a C l , 5.6 mM-KCI, 1.2 mM-MgCl,, 2 . 2 mM-CaCI,, 1.2 mM-NaH,P04, 20 mM-NaHCO,,, 5.5 mwglucose, 10 mMtheophylline, and bubbled with 95% 02-5% CO, gas. After equilibration, the ganglia are transferred to solutions containing KCl (15-100 mM) substituted for NaCl for 6 min. The ganglia are then homogenized in 6% trichloroacetic acid, and the homogenate is separated into supernatant and particulate fractions by centrifugation. After extraction with water-saturated ether, the supernatant solution is used for the radioimmunoassay of acety-