Drug treatments which influence brain serotonergic systems were administered to lactating female mice during the early postpartum period, and their effects on aggressive behavior, locomotor activity and brain monoamines were examined. P-chlorophenylalanine (200 and 400 mg/kg) and 5-hydroxytryptophan (100 mg/kg) inhibited fighting behavior of postpartum mice toward unfamiliar male intruder mice. These drug-treated postpartum females showed increased latencies to attack male intruders and also reduced frequencies of attack. In addition, postpartum mice treated with the serotonin receptor antagonists, mianserin (2 and 4 mg/kg), methysergide (4 mg/kg) and methiothepin (0.25 and 0.5 mg/kg), displayed significantly less aggressive behavior than control mice, as measured by reduced number of attacks. Whole brain monoamine and monoamine metabolite levels were measured after drug treatments. The behavioral results are discussed in terms of drug-induced changes in brain chemistry and indicate a possible role for serotonin in the mediation of maternal aggressive behavior of mice.