Serial blood samples were collected from anaesthetized spayed guinea-pigs subjected to anterior hypothalamic stimulation or injected with luteinizing hormone-releasing hormone (LH-RH), and the effect on the secretion of follicle-stimulating hormone (FSH) and LH followed. 2. Hypothalamic stimulation enhanced LH secretion, although the response waned during the course of the 1 hr period of stimulation; the secretion of FSH was not increased. After stimulation, FSH and LH levels fell below control values. 3. The response to stimulation of the hypothalamus was greater 2 weeks after spaying than after 1 week. 4. Since repeated periods of hypothalamic stimulation induced repeated surges of LH secretion, the decline in LH secretion during stimulation was not likely to have resulted from hypothalamic damage, while the observation that the plasma concentration of FSH and LH declined below control values after brain stimulation implies the operation of inhibitory mechanisms. 5. Pre-treatment of spayed guinea-pigs with progesterone depressed the resting plasma concentration of LH but did not affect the immediate response to hypothalamic stimulation. After hypothalamic stimulation the plasma gonadotrophin levels did not fall below control values. 6. Pre-treatment with oestradiol benzoate depressed the resting plasma level of LH and slightly reduced the size of the LH surge produced by hypothalamic stimulation. However, the raised plasma LH concentration was sustained after stimulation ended. 7. The response to hypothalamic stimulation after pre-treatment with progesterone and oestradiol benzoate showed features of the reaction to each steroid given singly. 8. The I.V. injection of 0-5 microng LH-RH induced a surge of LH secretions without affecting FSH discharge. 9. Pre-treatment with progesterone did not greatly modify the response to LH-RH but after an injection of oestradiol the high level of LH produced by the releasing factor was sustained for about 2 hr. 10. Injections of LH-RH during the phase of depressed LH release after hypothalamic stimulation produced a surge of LH secretion which matched that seen in non-stimulated animals.
