SUMMARY: The ultrastructure and hormone content of the paraventricular nucleus was studied in female rats after surgical isolation of the hypothalamus (by preparation of hypothalamic islands) from the rest of the brain for 48 h. When compared with control animals no quantitative changes were observed in the proportion of cytoplasm occupied by endoplasmic reticulum, Golgi apparatus and mitochondria or in the number of lysosomes/100 μm2 of cytoplasm. However, there was a very significant (P < 0·001) increase in the number of neurosecretory granules observed in the perikarya of paraventricular cells in the deafferentated preparations. Bioassay of hypothalamic extracts for milk ejection and antidiuretic activities showed that there was a significant increase (P < 0·05) of the former in hypothalamic islands. The increase was greatest in the paraventricular region (P < 0·01). The hypothalamic content of antidiuretic activity was not changed significantly by deafferentation. The results demonstrate that the amount of milk-ejection activity in the paraventricular nucleus is related to the number of neurosecretory granules and raises the intriguing question of why deafferentation of the hypothalamus influences its milk-ejection activity more than its antidiuretic activity.