5-HT1A receptor agonists have been shown to be effective clinically in the treatment of depression and anxiety. Flesinoxan is an example which is highly selective for the 5-HT1A receptor subtype. The objective of this study was to appraise the antidepressant potential of flesinoxan (1 and 3 mg/kg s.c.) in three tests which are indicative of antidepressant activity. These are (1) the forced swim test, following sub-acute administration, (2) 'open field' activity in the olfactory bulbectomised (OB) rat, following chronic administration, and (3) 8-OH-DPAT-induced hypothemia following chronic treatment. Both doses of flesinoxan significantly reduced the immobility time in the sham and OB groups when compared to their respective controls. In the 'open field', there was a significant increase in the ambulation of the OB control group. The higher dose of flesinoxan significantly reduced this deficit. In addition both doses of flesinoxan significantly attenuated the 8-OH-DPAT induced hypothermic response. These effects of flesinoxan are quantitatively similar to those seen following the chronic administration of antidepressants. These studies illustrate the potential antidepressant properties of flesinoxan, and hence further emphasise the role of the 5-HT1A receptor in the pathogenesis of depression. (C) 1997 Elsevier Science B.V.