Human neutrophils were demonstrated to possess interleukin-2 receptor (IL-2R) beta and gamma chains, not alpha chain and the binding of IL-2 to the IL-2R beta chain on neutrophils plays an important regulatory role in neutrophil functions. We have investigated in this study the hypothesis that recombinant human IL-2 (rhIL-2) can directly activate human neutrophils and increase their adherence to human umbilical vein endothelial cells (HUVEC). In an in vitro microtiter adherence assay, rhIL-2 significantly stimulated neutrophil adherence to HUVEC in a dose- and time-dependent manner, rhILI-2 concentration at 2000 u/ml and 2 hour incubation gave the best neutrophil stimulation. Treatment of neutrophils with rhIL-2 increased the expression of adhesion molecule CD18. Pretreatment of the stimulated neutrophils with a blocking monoclonal antibody to CD18 decreased but not completely blocked the adherence of neutrophils to HUVEC. These data suggest than rhIL-2 can directly stimulate and increase neutrophil adherence to HUVEC by enhancing the expression of CD18 and possibly other adhesion molecules on neutrophil surface. This may be a critical step in the early stage of the vascular leak syndrome (VLS) associated with high dose IL-2 therapy.