The effect of inescapable footshock stress on open-field activity, as measured by the number of ambulations, was studied in male mice. Ambulations significantly increased after footshock stress, the most significant effect appeared after 20 min-stimulation and the effect decreased as footshock time lengthened. The footshock stress-induced enhancement of ambulation was inhibited by haloperidol (0.2, 0.5 and 1 mg/kg), phentolamine (5 and 10 mg/kg), mianserin (20 mg/kg), atropine (0.5, 1 and 2 mg/kg), naltrexone (10 mg/kg) and MK-801 (0.05, 0.1 and 0.2 mg/kg), but was not influenced by propranolol (5, 10 and 20 mg/kg) or diazepam (1, 2 and 5 mg/kg). Haloperidol (0.5 and 1 mg/kg) and mianserin (5, 10 and 20 mg/kg) also exerted an inhibitory effect on non-stressed normal mice. These results suggest that dopaminergic, alpha-adrenergic, cholinergic, opioidergic and N-methyl-D-aspartate (NMDA) receptor-mediated neurotransmission systems are involved in the footshock stress-induced ambulatory activation.