AbstractA recently described social interaction (SI) model which is sensitive to single doses of benzodiazepines and novel non‐sedative anxiolytic agents has been used. Activities of drugs were compared in both an anxious (animals housed in pairs, tested with a novel partner) and a non‐anxious (animals housed in pairs, tested with the cage mate) condition. Diazepam displays a typical anxiolytic response, increasing SI in the anxious but not in the non‐anxious condition. This was associated with a decrease in aggression (AGG) and in locomotion (LOCO) at higher doses. Seven agents were tested which are thought to enhance central nervous system γ‐aminobutyric acid (GABA)‐mediated neurotransmission by increasing the activity of a receptor‐coupled chloride ionophore system as a major component of their action. Tracazolate, RL348, methaqualone, etomidate, LY81067, and pentobarbitone all significantly increased SI in the anxious but not the non‐anxious condition. In the anxious condition tracazolate and RL348 reduced AGG and all of these compounds except LY81067 reduced LOCO. Methaqualone and etomidate also reduced LOCO in the non‐anxious condition. In addition, an agent which reduces GABA function (picrotoxin) significantly reduced SI in already‐anxious animals, consistent with its known anxiogenic properties. Picrotoxin also reduced LOCO in both conditions. Phenobarbitone induced a non‐specific effect on SI (increased SI in both anxious and non‐anxious conditions), as well as reducing AGG in the anxious condition and LOCO in both conditions. These data suggest that agents enhancing GABA receptor‐coupled chloride ionophore function possess anxiolytic properties which may be att