The critical flicker fusion threshold (CFFT) is thought to index alertness and cortical arousal. Sedative drugs reduce CFFT while psychostimulants increase it. Procyclidine is an anticholinergic that is used to control the extrapyramidal side-effects of antipsychotics in schizophrenia. This study examined the effects of clinically relevant doses of oral procyclidine administration on CFFT and heart rate in two separate experiments (Experiment 1, drug dose: 10 mg, n = 16; Experiment 2, drug dose: 15 mg, n = 12) involving healthy subjects using a double-blind, placebo-controlled, cross-over design. 10 mg procyclidine had no significant effect on CFFT, heart rate or self-ratings of mood, but the 15 mg dose significantly lowered CFFT at 1 h and 2 h after procyclidine administration, increased drowsiness ratings and produced a drop in heart rate. The effects observed in this study may have implications for treatment compliance of schizophrenic patients, choice of antipsychotics, prescribing to patients with heart disease and monitoring of cardiac function under treatment. Further investigations are required to quantify the effects of procyclidine on CFFT and cardiac function in patients with schizophrenia.