Using immunohistochemistry and in situ hybridization the effect of nerve injury and of hormones was analysed in sensory and hypothalamic systems and in the pituitary gland. After peripheral axotomy a marked increase in NOS protein and mRNA levels was observed in dorsal root ganglia, the trigeminal ganglion and a less dramatic effect in the nodose ganglia. This effect lasted in the dorsal root ganglion neurons for at least 10 weeks. In the hypothalamic magnocellular neurons a transient increase was observed in the paraventricular and supraoptic nuclei. A similar effect was also seen after salt loading. In the anterior pituitary gland NOS was expressed in gonadotrophs and folliculo-stellate cells. Castration markedly increased NOS levels in the anterior lobe, and this could be counteracted by steroid hormone replacement. Thus, the present results show that the constitutive, neuronal NOS can be dramatically regulated in response to various manipulations, suggesting an important involvement of NO in these situations.