The purpose of the present study was to further evaluate the tail-temperature test as a tool to test potential steroidal and non-steroidal compounds for the treatment of hot flushes. Ovariectomized rats were implanted with a temperature sensitive probe. After a recovery period of 5 weeks, the effect of oestradiol (given via a silastic tube) and the 5-HT 2 receptor antagonist mirtazapine (10 mg/kg i.p.) on the tail-temperature in the active phase of the animals was measured. Oestradiol completely restored the disturbed tail temperature after 3 days. Treatment with mirtazapine also restored the oestrogen withdrawal-induced disturbed tail-temperature. The effect of mirtazapine was already seen on the first day of treatment. These experiments confirm and extend the idea that measuring the oestradiol withdrawal-induced disturbance of tail-temperature may be a useful tool to select compounds that might have beneficial effects in the treatment of hot flushes. Blockade of the 5-HT 2A receptors prevented or reduced the ovariectomy-induced disturbance of the rat tail-temperature, which may validate this model to evaluate the effect of compounds on hot flushes.