Naegleria fowleri is the common etiologic agent of primary amebic meningoencephalitis (PAM). We investigated the interaction of human neutrophils with Naegleria trophozoites and examined the effect of neutrophil stimulation by the recombinant human tumor necrosis factor (TNF) on this interaction. As indicated by scanning and transmission electron microscopy, TNF stimulated the adherence of neutrophils to N. fowleri with destruction of the ameba. Neutrophil iodination, an indirect measure of stimulation, increased from 0.81 ± 0.23 nmol/107 cells/hr to 2.41 ± 0.62 nmol/107 cells/hr following the addition of TNF to the neutrophil-N. fowleri mixture (P < 0.05). This was independent of complement or specific immunoglobulin. Ingestion of neutrophils by Naegleria trophozoites was observed following more prolonged incubation, particularly in the absence of TNF. These findings suggest a role for TNF-mediated destruction of Naegleria trophozoites by neutrophils in host defense, and that ingestion of host neutrophils by Naegleria trophozoites may represent a virulence factor.