The K+ current response to bath-applied adenosine has been studied on follicle-enclosed full grown oocytes from Xenopus laevis, using the two electrodes voltage-clamp technique. The response to adenosine was mimicked by forskolin, an activator of adenylate cyclase. Forskolin applied at low concentration potentiated the response to adenosine. At low concentration, isoprenaline, a beta-adrenergic agonist known to induce a potassium current via a rise of adenosine 3',5'-phosphate (cyclic AMP) into the oocyte, potentiated the response to adenosine. Progesterone (10(-5) M) reversibly induced a slight decrease (-24%) of the response to adenosine. The calcium ionophore A23187 applied in normal external medium reduced the response to adenosine (about -70%). Intracellular injection of EGTA induced an increase (+64%) of the peak response to adenosine. Acetylcholine (0.5-10 microM) inhibited the response to 3-10 microM adenosine by 44-91%. This inhibition was suppressed by atropine and was seen even on cells which did not show any current in response to acetylcholine application. The inhibition by ACh of the sensitivity to adenosine was long lasting (more than 1 h after the wash-out of ACh). A long term inhibition (-28 to -90%) also occurred when ACh was applied alone and washed before adenosine application. It is concluded that in Xenopus oocyte: increased cyclic AMP synthesis mediates the potassium response to adenosine; intracellular calcium ion concentration modulates this response; muscarinic stimulation induces a long-lasting inhibition of the sensitivity to adenosine.