This study examined whether the antidepressant-like effect of serotonin (5-HT)1A receptor agonists in the forced swim test (FST) is mediated by 5-HT1A receptors. The 5-HT1A receptor agonists 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and buspirone decreased immobility in the FST. The effect of 8-OH-DPAT was blocked by the 5-HT1A receptor antagonists NAN 190, BMY 7378 and pindolol. The effect of buspirone was blocked by NAN 190 and pindolol. The antagonists produced no effects on their own. The norepinephrine (NE) uptake inhibitor desipramine (DMI) also reduced immobility, and this was also blocked by NAN 190, BMY 7378 and pindolol. The alpha 1, beta 1 and beta 2 adrenergic antagonists prazosin, betaxolol and ICI 118,551 did not block either 8-OH-DPAT or DMI, and produced no effects on their own. These results provide evidence that the antidepressant-like effects of 5-HT1A receptor agonists in the FST are mediated through 5-HT1A receptors, probably located postsynaptically. The finding that the 5-HT1A receptor antagonists blocked the effect of DMI suggests that the NE and 5-HT systems interact in the FST.