The interaction of P. pseudomallei with human polymorphonuclear leukocytes (PMN) was examined. Human PMN ingested P. pseudomallei after incubation for 60 min in the presence of normal serum. The bacteria were relatively resistant to phagocytosis by human PMN in the absence of serum or in the presence of heat-inactivated serum (56.degree. for 30 min). Rapid intracelluar killing of P. pseudomallei was observed in the presence of 10% normal human serum; killing efficiency was reduced in the presence of heat-inactivated serum. Killing in the leukocyte bactericidal assay was predominantly due to the PMN bactericidal effect, not to the 10% normal serum contained in the incubation mixture. Ingestion of the bacteria was accompanied by a 2-fold stimulation of the hexose monophosphate pathway (HMP). In the absence of phagocytosis, the bacteria failed to show a marked enhancement in the HMP-shunt activity. EM evidence showed that degranulation and bacterial morphologic changes occurred within 1 h after the organism was ingested. Apparently, human PMN kill P. pseudomallei efficiently after ingestion of the organism in the presence of thermolabile serum opsonins. The occasional chronic nature of the disease caused by P. pseudomallei, therefore, can not be explained simply by the ability of the organism to survive within PMN.