The present study demonstrates the application of fMRI technology to neuropharmacology and the interaction of drug/receptor in the rat brain. Specifically, we have observed two different types of fMRI signal changes induced by acute i.v. heroin administration in rat brains under conditions of spontaneous and artificial respiration. Under spontaneous respiration, a global decrease in fMRI signal was observed; under artificial respiration, a region-specific increase in fMRI signal was identified and the activation sites are consistent with the distribution of opiate mu-receptors in rat brain as previously reported by autoradiography. Both heroin-induced fMRI signal changes were suppressed by pretreatment of naloxone, an opiate mu-receptor antagonist, and reversed by injection of naloxone following heroin infusion. These results suggest that fMRI has specific advantages in spatial and temporal resolution for studies of neuropharmacology and drugs of abuse.