<p>To date, benzodiazepine tranquilizers are the most widespread drugs, whose therapeutic effect is mediated by their binding with the allosteric binding site of GABA receptors. Despite the relatively high efficiency of benzodiazepines, they have side sedative and myorelaxant effects. Optimization of therapy for anxiety disorders based on use of benzodiazepines remains to be an actual problem. The aim of the present study was to revise in experiment the efficacy and safety of the combined treatment with benzodiazepine tranquilizers and selank, a peptide anxiolytic, registered in the Russian Federation. This study was performed in male Balb/c mice with enhanced basic anxiety. All drugs were injected intraperitoneally. The combined treatment with diazepam or mezapam and selank increased the number of entries and time spent in open arms of the elevated plus maze compared to the animals treated with tranquilizers only. This effect was probably due to the improvement of the anxiolytic effect of tranquilizers by selank or the antisedative effect of the peptide drug. To further clarify the mechanism of this effect, we studied mouse locomotor activity in the non-stressing conditions of a Rat-O-Matic automatic system. Under these conditions, selank prevented a decline of locomotor activity in mice treated with therapeutic doses of diazepam or olanzapine but not of haloperidol. Thus, it has been shown in animal experiments that selank enhances the anxiolytic effect and decreases the sedative and myorelaxant action of benzodiazepine tranquilizers.</p>