Administration of hypertonic NaCl solutions by intraperitoneal injection evokes a transient expression of immediate-early genes in the hypothalamic magnocellular neurons of supraoptic nuclei (SON), which is followed by an upregulation of arginine vasopressin synthesis and a general increase in cellular metabolic activity. Here we have analysed the changes that occur in the nucleus of SON neurons during the period of transient Fos expression after injection of hypertonic saline. Within the first 30 minutes after injection, the nuclei become significantly smaller, contain more condensed chromatin and incorporate less 3H-uridine than the controls. By 12 hours these effects are reverting and at 24 hours the nuclei are already more active than the controls. Additionally, we observe an initial decrease in the number of coiled bodies per nucleus within the first 2 hours, followed by a 3-fold increase at 24 hours after injection. As coiled bodies are transcription-dependent subnuclear ‘organelles’, these results further support the view that injection of hypertonic saline causes a transient inhibition of nuclear activity. Our data show that SON neurons respond to acute osmotic/stress stimuli first with inhibition and then with activation of gene expression. Importantly, inhibition of transcriptional activity occurs simultaneously with maximal accumulation of Fos protein in the nucleus, raising the possibility that activation of c-fos expression may cause repression of target genes.