Synaptosomal preparations from the motor area of the cerebral cortex of normocapnic, normoxic or hypoxic untreated beagle dogs and phenobarbital-, papaverine-, and (-) eburnamonine-treated dogs were incubated for 10 min at 24 degrees C and analyzed for ATP, ADP, AMP creatine phosphate, pyruvate, and lactate. The data were compared with those obtained from the whole controlateral cortical motor area, by the surface-freezing technique. Both during normoxia and after hypoxic hypoxia (15 min, at PaO2 equal to 17-19 mm Hg) the metabolite contents and ratios were very different in the incubated synaptosomal preparations and in the whole cerebral tissues. As concerns the drug treatment, papaverine was always inactive, while (1) eburnamonine increased the synaptosomal phosphorylation state in hypoxic dogs, being ineffective on the glycolytic metabolites evaluated. Phenobarbital increased the synaptosomal phosphorylation state both in normoxic and in hypoxic animals, and was effective also on the glycolytic metabolites studied.