There is evidence for reciprocal interactions between the brain monoamine neurotransmitters serotonin and noradrenaline which may play a critical role in homeostasis. The aim of the present study was to establish the effect of drug-induced damage to the serotoninergic system on noradrenergic activity in the hypothalamus. Bilateral intracerebroventricular injections of p-chlorophenylalanine (PCPA; 3 mg/kg in 2 x 6 microliters) were made to induce destruction in the serotoninergic system. Relative to saline-injected controls, PCPA-injected rats began overeating by 3 days postinjection. On day 10, when the experimental rats were consuming approximately 120% that of controls, animals were 4-h food deprived, sacrificed and the medial basal hypothalamus was removed for later analysis (by gas chromatography/mass spectrometry) of noradrenaline (NA), serotonin (5-HT) and dopamine (DA) and their principal metabolites dihydroxyphenylethyleneglycol (DHPG), 5-hydroxyindoleacetic acid (5-HIAA) and 3,4-dihydroxyphenylacetic acid (DOPAC), respectively. The ratio of metabolite to monoamine provided an index of functional activity. Trunk blood was collected for analysis of serum insulin and glucose. PCPA-injected animals had higher levels of DHPG (P less than 0.05), an increase in the DHPG/NA ratio (P less than 0.02), lower serum insulin (P less than 0.05) and increased serum glucose (P less than 0.05). There were significant correlations between noradrenergic activity (DHPG/NA ratio) and: (1) food intake (day 9 and 10 average; r = 0.62, P less than 0.05); and (2) serum glucose (r = 0.59, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)