Infection by pneumococci causes an acute inflammatory response associated with neutrophil influx, increased vascular permeability, and edema. Vascular endothelial growth factor (VEGF) is one of the most potent regulators of endothelial permeability. In vitro stimulation of neutrophils showed that pneumococci and purified pneumococcal cell wall induce VEGF secretion, independent of the presence of pneumolysin or polysaccharide capsule. The results of this study indicate VEGF is secreted in pneumococcal disease, suggesting a role as a mediator of increased vascular permeability.