Corticosteroid compounds are used broadly in surgical practice, although mechanisms remain unclarified and efficacy in some situations remains unproved. A recognized adverse effect of steroids in all doses is the potentiation of infection. Specific derivatives of the glucocorticoids appear to have varying degrees of effectiveness in the enhancement of bacterial infection. To evaluate such effects objectively, a series of experiments was undertaken to measure the phagocytic-bactericidal activity of polymorphonuclear leukocytes. This study examines the differential effects of clinical dose equivalents of four glucocorticoid derivatives in depressing in vitro neutrophil phagocytic-bactericidal function. Neutrophils separated from normal human plasma were incubated in vitro in the presence of hydrocortisone sodium phosphate, hydrocortisone sodium succinate, dexamethasone sodium phosphate, and methylprednisolone sodium succinate. Hydrocortisone sodium phosphate, hydrocortisone sodium succinate, and dexamethasone sodium phosphate produce variable, short-term inhibitory effects upon the systems within the neutrophil which are responsible for its bactericidal competency. Methylprednisolone sodium succinate appears to be free of these adverse effects. These in vitro experiments indicate that diminished risk of infection should attend the use of methylprednisolone sodium succinate, although the precise mechanism have not been defined.