A new histochemical method was developed for the detection of adenylate cyclase (AC) by stimulation of the enzyme activity with forskolin. This method was compared with the technique in which isoproterenol and 5-guanylylimidodiphosphate (GppNp) were used as activators of AC. The studies revealed that forskolin is not only a suitable activator of AC but is more effective than isoproterenol and GppNp for the demonstration of this enzyme histochemically. The availability of the method for the detection of AC activity without the necessity of using a hormonal stimulator has a great potential for the evaluation of this enzyme in normal and pathological tissues especially in those cases showing an absence or desensitization of the specific hormonal receptor linkage to AC.