Objective:To determine whether hydrocortisone given intravenously inhibits reactive oxygen species (ROS) generation by polymorphonuclear neutrophils (PMNLs)in vivoand, if so, to describe the pharmacodynamics of this effect.Design:A prospective, open label study in normal subjects.Setting:A clinical research unit of a tertiary referral center for diabetes and endocrinology.Patients:Eight normal subjects (age range, 24-50 yrs).Intervention:An indwelling cannula was inserted into the antecubital vein. Sequential blood samples were obtained from the cannula just before, and after, the intravenous injection of hydrocortisone (100 mg) at 1, 2, 4, 8, and 24 hrs.Measurements and Main Results:ROS generation by PMNLs and mononuclear cells (MNCs) was assayed as previously observed in a chemiluminometer. ROS generation by PMNLs and MNCs was inhibited by hydrocortisone at 1 hr; this effect peaked at 2 hrs and began to recover by 4 hrs; ROS generation had recovered to the baseline by 24 hrs. Although the pharmacodynamic effect of hydrocortisone on PMNLs and MNCs was similar, the peak inhibition was significantly greater for PMNLs (26% of basal vs. 43% of basal,p< .02) than MNCs.Conclusions:There is a marked, consistent, inhibition of ROS generation by PMNLs, which parallels that of MNCs after intravenous hydrocortisone. The pharmacodynamics of this effect are consistent with our current clinical practices.