In rats, the injection of soman (70 μg/kg, SC) resulted in a 90% inhibition of the cholinesterase (ChE) activities in three brain regions. The density ( B max ) for muscarinic acetylcholine receptors (mAChRs) following a single injection of soman was significantly reduced at 2 h after injection in the cortex and hindbrain. B max values, however, returned to baseline within 24 h. Subacute (repeated injection every 15 min) treatment with a sublethal dose of soman over 2 h also decreased the density of mAChRs. In both cases the density of mAChRs was reduced by about 15% for the cortex and 17% for the hindbrain (the midbrain was also reduced by 18% for subacute injections). Chronic administration (once daily for 7 days) of soman (20 μg/kg, SC) produced maximal inhibition of ChE activity but did not significantly downregulate mAChRs. Clonidine pretreatment reversed the soman-induced mAChR downregulation in cortex and hindbrain produced by acute soman administration. Thus, marked reduction in the levels of brain ChE is not the only factor involved in the production of mAChR downregulation to cholinesterase inhibitors.