Oestrogen, acting in both the brain and pituitary, has a critical role in regulating the reproductive cycle in most mammals. In the brain, oestrogen regulates the release of luteinizing hormone-releasing hormone (LHRH) partly through a mechanism that is blocked by inhibitors of DNA-dependent RNA synthesis or protein synthesis. The distributions of oestrogen-concentrating neurones and of LHRH neurones overlap. The present study was undertaken to determine whether genomic effects of oestrogen mediated by nuclear oestradiol concentration include a direct effect on LHRH-containing neurones. During extensive studies in which the immunocytochemical method for localizing LHRH neurones was optimized and made compatible with the autoradiographic method for detecting oestrogen-concentrating neurones, doubly-labelled cells were very rarely seen. This suggests that genomic regulatory effects of oestrogen which depend on nuclear retention are not exerted directly on most LHRH neurones, but rather must be mediated by another class of neurones.