Rats were exposed to 21, 8 or 6% O2 or to 8% O2 with 5% CO2. After 30 min equilibration, groups of normoxic and hypoxic rats received electrical foot shocks for 15 min through a grid floor. The initial, rate-limiting steps in brain monoamine synthesis were measuredin vivo by determining the accumulation in different brain regions of dopa and 5-hydroxytryptophan (5-HTP), induced by the inhibitor of the aromatic amino acid decarboxylase, NSD 1015 (3-hydroxybenzylhydrazine HCl 100 mg/kg i.p.). In other rat groups a different approach to measuring catecholamine turnover was used, i.e. the depletion of brain dopamine and noradrenaline, induced by the tyrosine hydroxylase inhibitorα-methyltyrosine (400 mg/kg of the methylester HCl i.p.). Hypoxia retarded the formation of dopa and 5-HTP. Shock had the opposite action, though with considerable regional differences with respect to dopa formation. The effect of shock on dopa formation was still present under hypoxia, whereas the effect on 5-HTP formation was completely prevented. Hypercapnia reversed the effect of hypoxia on dopa formation but left 5-HTP formation unchanged. The depletion of dopamine and noradrenaline, induced byα-methyl-tyrosine, was enhanced by shock, but the effect was completely prevented by moderate hypoxia. While hypoxia may in part influence monoamine metabolism directly, by reducing the availability of oxygen for oxidative processes, the biochemical consequences of changes in physiological neuronal activities probably contribute to the overall effect and especially to the complex interaction between hypoxia and shock stress.