We demonstrate for the first time that recombinant human monocyte interleukin-8 (rhMIL-8) primes human neutrophil responses to fMLP. Human neutrophils preincubated for 10 min with 10(-8) M rhMIL-8 and then stimulated with micromolar fMLP show enhanced release of superoxide anions, platelet-activating factor (PAF) and arachidonic acid compared with cells which are not initially exposed to rhMIL-8. We also demonstrate that this enhancement of the neutrophil response is dependent on the dose of rhMIL-8 with the greatest enhancement corresponding with IL-8 levels which cause maximum shape change of neutrophils. Priming of neutrophils occurred after only 30 seconds preincubation with rhMIL-8 indicating that the mechanism of IL-8 priming is extremely rapid as was stimulation of neutrophil shape change by rhMIL-8. Priming of neutrophils with rhMIL-8 did not increase sensitivity to fMLP but enhanced responsiveness to activating concentrations. rhMIL-8 alone at levels used for priming caused no release of superoxide anions, arachidonic acid or PAF. These results suggest that IL-8 primes neutrophil phospholipase A2 and NADPH-oxidase activation in response to fMLP.