The mechanisms underlying corticosteroid-induced neutrophil leukocytosis are not fully understood; however, leukocyte/endothelial cell adhesion molecule interactions are known to be key to the movement of neutrophils within and out of the vasculature. This study was designed to investigate the effects of corticosteroids on neutrophil adhesion molecules in relation to neutrophil leukocytosis. Circulating neutrophil counts, neutrophil L-selectin and Mac-1 expression (measured by flow cytometry), soluble L-selectin, and granulocyte-colony stimulating factor concentrations were determined in 15 multiple sclerosis patients receiving intravenous methylprednisolone prior to and at 6 and 24 h following the initial 500-mg dose. A follow-up sample was obtained 48 h after the 5-day therapeutic course. Neutrophil counts were elevated at 6 h (threefold) and 24 h (twofold). This was associated with a 40% reduction in L-selectin expression at 6 and 24 h and a 35% reduction in Mac-1 expression at 6 h. Serum granulocyte-colony stimulating factor levels were increased (6 h: threefold; 24 h: twofold), whereas soluble L-selectin concentrations were unaltered. All of the above parameters had returned to basal levels in the follow-up sample. Short-term in vitro cultures (6 and 24 h) of blood samples from untreated multiple sclerosis patients and controls with 0.01 mg/ml methylprednisolone resulted in minimal reductions in neutrophil L-selectin and Mac-1 and no change in soluble L-selectin. Granulocyte-colony stimulating factor induced Mac-1 expression in a dose-dependent manner, whereas L-selectin expression was unaffected or reduced at high concentrations. Reduction in neutrophil L-selectin and Mac-1 expression following methylprednisolone infusion may cause decreased adhesion of marginated neutrophils and/or reduced capacity of neutrophils to migrate from the vasculature. Additionally, the induction of granulocyte-colony stimulating factor may contribute to neutrophil production and release into the circulation.