A pharmacological study was undertaken to evaluate the role of catecholamines and serotonin in the mediation of aggression. The dose-effect relationship of d-amphetamine, apomorphine, methysergide, lisuride, and the time-dependent effects of 10 mg/kg p-chloroamphetamine (PCA) were determined on aggressive behavior in a habituation paradigm. The frequency of attacks and sideways threats exponentially declined in ten consecutive confrontations between resident and intruder mice, and recovered when a new intruder was introduced. d-Amphetamine (0.1-5.0 mg/kg) and apomorphine (0.03-1.0 mg/kg), administered IP 5 min before the first confrontation, attenuated the usual decline of attack and threat in subsequent trials. PCA enhanced attack, sideways threat, and locomotion at day 1 after injection. Methysergide (1, 3, 10 mg/kg) and lisuride (0.03, 0.3, 1.0 mg/kg) suppressed all activity, including locomotion and aggression. The data support the hypothesis that catecholamines mediate the activation of aggression, but do not indicate an inhibitory role for serotonin. Aggression in the resident-intruder paradigm appears to require intact serotonin activity.