The use of pulsatile GnRH to treat infertile women who do not ovulate has been shown to be safe, simple, and effective and the preferred method of inducing ovulation in appropriately selected patients who are resistant to treatment with clomiphene citrate. Treatment with GnRH is particularly effective for restoring ovulation in patients with idiopathic hypogonadotrophic hypogonadism and partially recovered weight-related amenorrhoea, but less successful in patients with polycystic ovary syndrome and organic hypothalamic pituitary disease. Based on personal experience, we advocate routine use of the subcutaneous route, using 15 micrograms per pulse every 90 min, and we monitor the patient's progress by serial ultrasound scanning and measurement of serum gonadotrophin and oestradiol concentrations. If the patient does not respond we recommend adding treatment with clomiphene citrate (Homburg et al, 1988b). Treatment with intravenous GnRH is reserved for women who do not respond to the above combination of drugs. We do not treat patients with GnRH until their body mass index is in the normal range (between 20-25) and we avoid GnRH treatment in patients with hypersecretion of LH during the follicular phase. If LH concentrations are raised, an alternative method of treatment is recommended, such as ovarian diathermy (Armar et al, 1990). Finally, the question of whether GnRH deficiency in patients with hypogonadotrophic hypogonadism is caused by a specific genetic lesion is not yet fully resolved. Yang-Feng et al (1986) used a cDNA clone encoding the human GnRH precursor molecule in order to assign the GnRH gene to a particular human chromosome. They found a single site for GnRH sequences in the human genome and that the gene coding for GnRH is located on the short arm of chromosome 8. Experiments in the congenitally hypogonadal mouse have shown that it is possible to restore gonadal development and gametogenesis by gene transfer (Mason et al, 1987). Clearly an abnormality at the level of the genome may be responsible for the secretory defect in patients with hypogonadotrophic hypogonadism, but it has yet to be defined (Weiss et al, 1989). Presumably elucidation awaits the development of more refined methods because both the genetics and the clinical associations of GnRH deficiency are most persuasive. Meanwhile replacement treatment with GnRH provides a simple and safe form of treatment for managing the clinical syndromes of GnRH deficiency.