The behavioral effects of cholinergic agonists and antagonists were examined in two lines of rats which have been developed through selective breeding techniques to be differentially sensitive to the anticholinesterase diisopropyl fluorophosphate (DFP). The line of rats which were determined to be more sensitive to DFP (Flinders S line) were also more sensitive to the depressant effects of the agonists pilocarpine and physostigmine on locomotor activity, water intake, and operant responding maintained by water reward. In contrast, the locomotor stimulant effects of scopolamine, a muscarinic antagonist, were less marked in the S-line rats, while the depressant effects of atropine and scopolamine on water intake and operant responding maintained by water reward were comparable in the two lines. The S-line rats were also significantly more sensitive to the hypothermic effects of pilocarpine and oxotremorine. These findings are consistent with the hypothesis that the S-line rats are more sensitive to the acute effects of DFP because they have a higher number of muscarinic-cholinergic receptors.