Adult male mice of the Swiss CD1 strain were used to evaluate the effects on isolation-induced aggressive behaviour of a single intravenous administration of substance P (SP; 0.25, 1.0 or 2.5mg/kg dose). All mice were injected 15min before testing (10min videotaped dyadic encounters with an isolated male untreated opponent). Control mice were injected with vehicle. All animals were tested again 24h later in a drug-free state. SP treatment produced a decrease in offensive scores (Attacks and Rattling behaviour), a longer latency to the first Attack episode, and enhanced defensive displays. These effects were reversed 24h later. In no case did SP treatment affect locomotor activity levels or freezing behaviour. A role of SP in the regulation of murine aggressive response is strongly suggested through a direct action of the drug on the central nervous system and specifically on the hypothalamus.