Male rats were exposed to the smoke from 2 cigarettes every morning for a total period of 9 days. The next day they were decapitated immediately after the exposure to the smoke from 4 cigarettes (Kentucky reference IR-1 type) burned at 30-min intervals. Control animals were exposed to air alone or to nicotine-free cigarette smoke (Cambridge glass fibre filters). In contrast to chronic exposure to filtered smoke, exposure to unfiltered smoke resulted in a 10% increase in catecholamine (CA) levels (quantitative histofluorimetry) within the lateral palisade zone, the posterior periventricular hypothalamic nucleus and within the dorsomedial hypothalamic nucleus. There was also an increase in amine turnover (tyrosine hydroxylase inhibition by α-methyl-dl-p-tyrosine methylester; αMT) in the dopamine (DA) systems of the medial and lateral palisade zones and in the periventricular noradrenaline (NA) hypothalamic systems. Chronic exposure to unfiltered cigarette smoke resulted in reductions of prolactin, LH and FSH levels (radioimmunoassay). Following αMT treatment chronic exposure to unfiltered cigarette smoke still led to reduced prolactin serum levels. In addition an increased vasopressin serum concentration was found. The effects of chronic exposure to cigarette smoke on neuroendo-crine function and on hypothalamic CA systems are suggested to be mediated via nicotine. Combined with the results from a previous study the present results indicate that tolerance does not develop with regard to the inhibitory effects of exposure to cigarette smoke on prolactin, LH and FSH secretions. The same is true for the stimulatory effects on the tubero-infundibular DA neurons and the periventricular NA systems. But chronic exposure to cigarette smoke seemed to induce tolerance with regard to its stimulatory effects on subependymal, dorsomedial and paraventricular hypothalamic NA systems and on corticosterone relea