Nitroblue tetrazolium (NBT) dye reduction by leukocytes of 21 patients receiving prednisone was significantly decreased. Nineteen percent of the patients had values similar to those found in children with chronic granulomatous disease, and 57% had heterozygous-range NBT dye reduction. A qualitative NBT dye reduction "slide test" correlated well with the quantitative assay. The uptake of particles by the phagocytes of steroid-treated patients appeared normal. The exact mechanism of corticosteroid action remains unknown. The decreased dye reduction observed in vitro suggests an induced defect of intracellular metabolism which may be related to known alterations of host defenses which occur in patients receiving these hormones.