In the present research the desensitization of adenylate cyclase system induced by isoproterenol (IPR), a beta-adrenergic agonist, in primary glial cell cultures and the effects of an exposure to 3-isobutyl-1-methylxanthine (IBMX) on the response to a subsequent stimulation with IPR have been investigated. A pretreatment with the phosphodiesterase inhibitor IBMX induced refractoriness to a subsequent IPR challenge suggesting a possible involvement of cAMP in heterologous desensitization. Moreover the present results show that IPR desensitized cells in confluent cultures retained a normal response to cholera toxin, while IBMX treated cells exhibited a reduced response to the toxin. So IPR induces a rather specific desensitization while IBMX induced refractoriness seems to be non specific.