Clinical case reports and survey data point to incidences of intense violence in certain individuals self-administering high doses of amphetamine via the intravenous route. It is unclear how common this amphetamine effect is, what circumstances promote its occurrence, and which characteristics predispose an individual to exhibit this effect. Amphetamine may engender a dose-dependent biphasic effect on aggressive behavior in experimental situations, both with human and animal subjects, as, for example, in subjects that have habituated to an aggression-provoking stimulus. Most often, however, amphetamines disrupt social, sexual, maternal, and aggressive behavior patterns in a dose-dependent manner; neither tolerance nor sensitization appears to develop to these disruptive effects. Amphetamine consistently enhances defensive and flight reactions in various experimental situations and animal species. This effect appears to be mediated by brain dopaminergic systems. So far, no dopaminergic, noradrenergic, or opioid antagonists have been found that attenuate, reverse, or prevent the disruptive effects of amphetamines on social and aggressive behavior. The evidence from opioid-withdrawn subjects strongly suggests a profound modulatory influence by opioid peptides on the aggression-altering effects of amphetamines.