Adrenal chromaffin cells have been found to accumulate ascorbic acid by a saturable high affinity mechanism that is inhibited by hydrocortisone. The rate of ascorbic acid transport into cells was linear for at least 1 h and had a Km of 103 microM, a value approaching the reported concentration of ascorbic acid in the adrenal vein during stress. The uptake process itself, representing net accumulation rather than exchange, was inhibited by 0 degrees C, lack of sodium, ouabain, and by dinitrophenol and iodoacetate. Hydrocortisone but not the inactive analogue hydrocortisone hemisuccinate was found to inhibit ascorbic acid uptake in a reversible manner, with an ID50 of 62 microM. This value was within the reported steroid concentration in the adrenal portal system during a significant stress. Both ascorbic acid and hydrocortisone are secreted from cortical cells during stress into the adrenal portal system and thus contact medullary chromaffin cells. We suggest that the control of ascorbic acid uptake by hydrocortisone indicates the existence of a heretofore unanticipated biochemical aspect of the adrenal stress response.