SUMMARY Experiments were conducted to examine the behavioural response of spayed heifers to oestrogen, and its modification by progesterone. In two groups of heifers, the median effective doses (MED) of oestradiol benzoate (ODB) were 121 and 132 μg. Repeated doses of ODB at physiological levels did not induce a state of refractoriness; in this respect the heifer is dissimilar to the ewe. However, repeated doses of 10 mg. ODB induced refractoriness to 400 μg. ODB. When such refractory heifers were treated with 10 mg. progesterone/day for 5 days, they showed a normal response to 400 μg. ODB given 3 days later. This return to normal sensitivity was not sustained, and pretreatment with progesterone was necessary for a normal response to subsequent small doses of ODB. The transient removal of the refractory state appears not to be due to a simple synergistic effect of residual progesterone, but to an effect of preconditioning a neural centre to respond to oestrogen. Increasing the duration of pretreatment with progesterone beyond 5 days did not result in a greater sensitivity to ODB. Pretreatment with progesterone in heifers not made refractory to ODB did not result in an increased sensitivity to ODB. Moreover, up to 7 days after termination of the progesterone treatment, the response to ODB was reduced and the slope of the dose-response line was less steep than when ODB was injected alone. The reduction of the response was more pronounced with 40 mg. progesterone/day than with 10 mg. The possible significance of these results in intact animals is discussed.