The effect of epicutaneous methyl prednisolone (MP) at 10-4, 10-5, and 10-6 molar concentration was studied in 54 normal, healthy volunteers using a new, in vivo microchemotaxis technique. Significant inhibition of monocyte chemotaxis occurred at all concentrations studied and persisted over a 24-hr period with 10-4 molar MP. Neutrophil chemotaxis was significantly inhibited only with 10-4 MP. The inhibitory effect of MP on neutrophil and monocyte chemotaxis occurred earlier and at lower concentrations if the skin sites were pretreated with steroid. Thus, when corticosteroids are applied on abraded skin in concentrations achievable in vivo, monocyte chemotaxis into tissue is inhibited for longer periods and at lower drug concentrations than is neutrophil chemotaxis. By avoiding the significant systemic effects of corticosteroids on circulating monocyte and neutrophil populations, these experiments establish that local inhibition of chemotaxis is an important anti-inflammatory effect of corticosteroids, with differential effect on monocytes and neutrophils.