The human supraoptic nucleus (SON) is the main production site of plasma arginine-vasopressin (AVP). The present study aimed to define the subpopulation of patients in which multinucleated SON neurons (MNN) are present. We determined the proportion of MNN in immunocytochemically defined SON AVP population and compared AVP mRNA levels in the SON of 29 patients with and without MNN. Interestingly, MNN appeared to be present in a high proportion in patients with pneumonia and other pulmonary pathologies (Pul P). The percentage of MNN in the SON of Pul P patients turned out to be age- and sex-dependent. In young women with Pul P their proportion was 10 times higher than in women without such a pathology and in young men with Pul P their frequency was 22 times higher than in other men. In those patients with the highest proportion of MNN, i.e. young females and males with Pul P, AVP mRNA expression in the SON was the lowest. In addition, young women (less than or = 50 years old) had lower AVP mRNA levels than young men and than elderly women (>50 years old). In conclusion, our study suggests that multinucleated neurons are a hallmark of Pul P in the human SON and that this phenomenon may be accompanied by lower AVP production in young subjects.