1 Exposure of guinea-pigs to a CO2-enriched atmosphere (20% CO2, 25% O2, 55% N2) for 1 to 5 h caused a marked, progressive increase of plasma dopamine beta-hydroxylase (DBH) activity which reached its peak after 2 h of CO2 exposure and then gradually decreased. The increase was abolished by mecamylamine administration before exposure in CO2. Plasma levels of noradrenaline (NA) also increased after CO2 exposure. 2 Guanethidine administration, before exposure to CO2, abolished the increase of plasma NA but potentiated the increase of circulating DBH. Phenoxybenzamine injection, before exposure to CO2, also potentiated the increase of plasma enzyme activity. In both cases, DBH activity was increased to almost 10 times the basal circulating enzyme levels. 3 Injection of 6-hydroxydopamine (6-OHDA) caused a pronounced decrease of DBH activity in the right atrium, thoracic aorta and spleen; the adrenal enzyme activity was unchanged. Exposure to CO2 of 6-OHDA-treated animals still evoked a dramatic increase of plasma DBH activity comparable to that found in control animals. 4 The increase of plasma DBH activity evoked by exposure to CO2 of adrenalectomized animals was considerably diminished. 5 These data suggest that in the guinea-pig, the adrenal is the main source of the increase of circulating DBH activity evoked by exposure of the animals to a CO2-enriched gas mixture.