Prior attempts to study adrenal medullary O2 metabolism during catecholamine secretion have been unsuccessful because venous blood from medulla mixes with venous blood from the much larger cortex. To circumvent this problem, eight adult mongrel dogs were pretreated for 5-6 wk with the adrenocorticolytic agent 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane (o,p'-DDD). Prednisolone (5 mg/day) and fludrocortisone (0.1 mg.10 kg-1.day-1) were administered orally to prevent adrenocortical insufficiency. Animals were then anesthetized with pentobarbital sodium and subjected to splanchnic nerve stimulation (NS) at 20 and 4 Hz to elicit catecholamine secretion. NS at 20 Hz increased epinephrine secretion from 1.6 +/- 0.7 to 1,780 +/- 762 ng.min-1.g medulla-1 but had no effect on medullary O2 consumption. Medullary blood flow (MQ) increased from 216 +/- 63 to 1,522 +/- 182 ml.min-1.100 g-1, and O2 extraction decreased from 2.7 +/- 0.7 to 0.8 +/- 0.2%. NS at 4 Hz increased epinephrine secretion from 3.1 +/- 1.4 to 76 +/- 17 ng.min-1.g medulla-1 and MQ from 226 +/- 66 to 649 +/- 122 ml.min-1.100 g-1 but had no effect on adrenal O2 consumption or extraction. Cortical blood flow was 342 +/- 98 ml.min-1.100 g-1 at baseline and was unaffected by NS. Gross weight of cortex was reduced by 80% in o,p'-DDD-treated animals, and histological examination of glands from three animals showed only rare islands of glomerulosa cells remaining. These data suggest that increases in MQ during NS do not occur in response to changes in O2 consumption.