Rats injected daily with haloperidol (0.15 mg/kg) failed to acquire a one-way avoidance response over a 9 day period (10 trails/day). When these animals were subsequently tested without haloperidol, on the first drug-free day they preformed as well as animals given saline throughout the training period and significantly better than naive saline-treated animals on the first day of training. The performance of rats which were trained for two days before receiving haloperidol was only partly blocked by the drug, while animals trained for 9 days before drug administration were immune to the disruptive effects. Three anticholinergic (muscarinic) drugs, atropine (10 mg/kg), scopolamine (1 mg/kg) and benztropine (2 mg/kg) significantly reversed the effect of haloperidol on the acquisition of the nigroneostriatal projection and support the view that this system is critically involved in the acquistion of learned instrumental responses. The nature of the avoidance deficit produced by these treatments is discussed with reference to the possibility that they selectively block the initiation of boluntary motor responses. According to this hypothesis, the failure of these teratments to disrupt escape responding may be due to the fact that the unconditioned stimulus generates reflexive motor responses (flinch, jump, etc.) which are sufficient to begin the motoric sequences that cannot be initiated voluntarily in response to the conditioned stimulus.