The effects of acute administration of an indirect dopamine-agonist, d-amphetamine, and a non-selective dopamine receptor antagonist, haloperidol, were investigated in normal male volunteers on habituation and prepulse inhibition (PPI) of the acoustic startle reflex in two experiments. In Experiment 1, 40 male non–smoker volunteers were tested for habituation and PPI (defined as percentage reduction of the pulse-alone amplitude; prepulses 9 dB above background) before and after double–blind administration of either 2mg haloperidol or placebo. No influence of haloperidol was observed on either habituation or PPI of the startle reflex in this experiment. In Experiment 2, 60 male volunteers underwent startle testing before and after double-blind administration of a single oral dose of 5 mg haloperidol, 5 mg damphetamine or placebo. Habituation and PPI (prepulses 15 dB above background) for the placebo group did not differ significantly from that observed for the rf-amphetamine or for the haloperidol group. However, in a subgroup of smoking subjects, both d-amphetamine and haloperidol reduced PPI as compared to that observed prior to drug administration. The implications of these findings in relation to animal pharmacological studies and observed sensorimotor gating deficits in schizophrenia are discussed. Behav Pharmacol 1998; 9:567— 576 © 1998 Lippincott Williams & Wilkins.