Prepulse inhibition (PPI) of the startle response refers to a reduction in response to a strong stimulus (pulse) if this is preceded shortly by a weak non-startling stimulus (prepulse). Consistent with theories of deficiencies in early stages of information processing, PPI is found to be reduced in patients with schizophrenia. Atypical antipsychotics are found to be more effective than typical antipsychotics in improving PPI in this population. Anticholinergic drugs are often used to control extrapyramidal symptoms induced by antipsychotic medication, especially by typical antipsychotics, in schizophrenic patients and are known to disrupt cognitive functions in both normal and schizophrenic populations. The effect of anticholinergics on PPI in schizophrenia has not yet been examined. This study determined the effects of procyclidine, an anticholinergic drug, on PPI in patients with schizophrenia given risperidone or quetiapine and not on any anticholinergic drugs, employing a placebo-controlled, cross-over design. Under double-blind conditions, subjects were administered oral 15 mg procyclidine and placebo on separate occasions, 2 weeks apart, and tested for acoustic PPI (prepulse 8 dB and 15 dB above the background and delivered with 30-ms, 60-ms and 120-ms prepulse-to-pulse intervals). Procyclidine significantly impaired PPI compared to placebo (assessed as percentage reduction) with 60-ms prepulse-to-pulse trials and increased the latencies to response peak across all trials. The use of anticholinergics needs to be carefully controlled/examined in investigations of information processing deficits using a PPI model and reduced to the minimum level in clinical care of schizophrenia.