Male rats were treated acutely with nicotine (4 × 2 mg/kg, 30-min time intervals, total treatment time 2 h) or exposed to cigarette smoke from 4 × 1 cigarette (30-min time intervals, total treatment time 2 h). Some rats were pretreated with the Dl dopamine (DA) receptor antagonist SCH 23390 (0.1–3.0 mg/kg, i.p.), or with the D2 DA receptor antagonists remoxipride and raclopride (1 mg/kg, i.p.), or with the 5-hydroxytryptamine 2 (5-HT2) receptor antagonist ketanserin (0.3 mg/kg, i.p.) 5 min before nicotine treatment or the acute intermittent exposure to cigarette smoke. Some rats were treated with the Dl DA receptor agonist SK&F 38393 (1–10 mg/kg, i.p.) 15 min, 30 min or 2 h before decapitation. Hypo-thalamic and pre-optic catecholamine (CA) levels were measured by quantitative histofluorimetry in discrete DA and noradrenaline (NA) nerve terminal systems. Serum thyroid-stimulating hormone (TSH), prolactin, luteinizing hormone (LH), follicle-stimulating hormone (FSH), vasopressin, corticosterone and testosterone levels were determined by radio-immunoassay procedures. Nicotine treatment and to a minor degree also acute intermittent exposure to cigarette smoke produced a reduction in serum prolactin, LH and TSH but not in serum FSH, vasopressin and testosterone levels. Nicotine treatment also increased serum corticosterone levels. Pretreatment with the Dl DA receptor antagonist SCH 23390 (1–3 mg/kg) counteracted the lowering of serum LH, but not of prolactin and TSH levels induced by nicotine or exposure to cigarette smoke. SCH 23390 alone (1–3 mg/kg) increased serum TSH levels. Remoxipride, raclopride or ketanserin did not counteract any of the neuro-endocrine actions induced by nicotine treatment. However, ketanserin alone lowered serum prolactin levels. SK&F 38393 increased serum TSH, prolactin and LH levels. It was found that nicotine treatment and exposure to cigarette smoke with few exceptions produced a depletion of CA stores in NA and DA nerve terminals of the hypothalamus, pre-optic area and median eminence which was counteracted by SCH 23390 (1 mg/kg) but not by remoxipride, raclopride (1 mg/kg) or ketanserin (0.3 mg/kg). The results indicate that Dl but not D2 DA or 5-HT2 receptors may modulate the NA and DA release in the median eminence, the hypothalamus and the pre-optic area induced by nicotinic cholinoceptor activation. Furthermore, Dl DA receptors in the median eminence may at least in part mediate the inhibitory effects of nicotine on LH but not on TSH and prolactin secretion, although there appears to exist a Dl DA receptor in the median eminence which inhibits TSH secretion. The results are in line with our hypothesis that activation of the tubero-infundibular DA neurons via Dl DA receptors mediates the inhibition of LH secretion caused by nicotine treatment or exposure to cigarette smoke. Finally, the facilitatory serotonergic mechanism on prolactin secretion is probably mediated via 5-HT2