A single administration of Th (10 and 20 mg/kg, p.o.) to adult male albino rats (140-150 gm b.wt.) enhanced adenylate cyclase activity in cerebral cortex (55-123%), cerebellum (85-115%), corpus striatum (18-40%), hypothalamus (32-66%) and in pons-medulla (13-25%). Treatment with Th (10 and 20 mg/kg/day, p.o.) for 4 consecutive days produced less increase in adenylate cyclase activity in cerebral cortex (12-42%), corpus striatum (20-24%), hypothalamus (12-29%) and in pons-medulla (20-37%) than that observed with single day Th. Unlike those regions of brain the cerebellar adenylate cyclase activity (120-157%) showed greater stimulation following 4 consecutive days of Th (10 and 20 mg/kg/day p.o.) treatment compared to one day treatment (85-115%) with Th (10 and 20 mg/kg, p.o.). Th (10 mg/kg/day, p.o.) under tolerant condition, unlike its nontolerant condition reduced adenylate cyclase activity in the all brain regions studied. These results thus suggest that (a) Th under nontolerant condition produced region specific inhibition of adenylate cyclase activity and hence central adenosinergic activity which may be a resultant effect of heterogenious distribution of extra-cellular adenosine receptor (A1 and A2) of different brain regions and also the availability of adenosine for interaction to the intracellular receptor sites (P-site) under this condition; (b) development of tolerance to Th may reduce the brain regional adenylate cyclase activity by increasing the A1 receptor population and hence may stimulate the central adenosinergic activity.