Representative agents from all of the major classes of drugs that have been reported to be selective antagonists of spontaneous mouse-killing behavior (i.e., antidepres-sants, antihistamines, anticholinergics, and stimulants) were tested for their ability to antagonize the mouse-killing response in rats that became killers following removal of the olfactory bulbs (O.B. lesion-induced killer rat) and in spontaneous killers. All of the drugs tested selectively antagonized the killing behavior of both spontaneous and lesion-induced mouse-killing rats. Several drugs (i.e., imipramine, amitriptyline, d-amphetamine, and chlorpheniramine) were found to be significantly less potent antagonists of mouse killing in the 0.6. lesioned rat as compared to spontaneous killers. Since all of the drugs that exhibited significant differences in activity between the two models have been shown to possess the ability to elevate norepinephrine levels at receptor sites in the brain, alterations in noradrenergic systems may account for the differences in sensitivity that were observed in this study. The possibility that there may be a common neural substrate for mouse killing in the two models is discussed.