Rats gonadectomized 1-2 months previously were anaesthetized with sodium pentobarbitone and 50 ng/100 g body weight of a synthetic decapeptide gonadotrophin releasing factor (LH-RF) injected intravenously. Palsma concentrations of LH and FSH were determined by radioimmunoassay in samples taken before and at intervals up to 60 min after injection of LH-RF. The pituitary response was evaluated by determining the maximal increment in plasma gonadotrophin concentrations and by estimating the area under the plasma gonadotrophin concentration curves. In both males and females the pituitary response was increased in animals given 20 mug oestradiol benzoate 3 days earlier. Progesterone (2-5 mg) had no effect on the response measured 4 h later in oil-treated rats, male or female. In oestrogen-primed rats progesterone administration produced a significantly increased response in females that was not seen if sodium pentobarbitone was given at the time of progesterone injection. In oestrogen-primed males progesterone produced some increase in sensitivity but less than was seen in females. Both in males and in females that had received androgen on day 4 of postnatal life sodium pentobarbitone had no effect on the responses of oestrogen plus progesterone-treated rats to LH-RF. When two injections of LH-RF were given 60 min apart, the second response was greater than the first in animals, both male and female, that had been primed with oestrogen. The second response was no greater than the first in oil-treated females. The results suggest that oestrogen can increase pituitary sensitivity of LH-RF in both male and female rats and that LH-RF itself can increase pituitary sensitivity to a second injection of LH-RF in both male and female rats if they have received oestrogen. It is suggested that the differences between the pituitary responses of females and males after oestrogen plus progesterone treatment and the major differences in gonadotrophin secretion reported previously (Brown-Grant, 1974) may be accounted for on the basis of there being a relatively slight increase in endogenous LH-RF secretion with a consequent marked rise in pituitary responsiveness in female but not in male rats.