Abnormalities of polymorphonuclear leukocyte (PMN) function contribute to high rates of postoperative infection in the newborn and to the vulnerability of newborns to overwhelming bacterial and fungal sepsis. The authors investigated (1) the effects of major surgery and sepsis on PMN chemotaxis in the newborn and (2) the role of cytoskeletal rearrangements in regulating chemotaxis. The subjects studied included newborns with sepsis (n = 16), newborns who underwent major surgery (n = 7), healthy full-term newborns (n = 21), and healthy adult volunteers (n = 28). Peak actin polymerisation was diminished in all newborns (relative to the adults) after stimulation with formyl methionyl leucyl phenylalanine (FMLP) (10 nmol/L), and with zymosan activated serum (ZAS) (10%). Major surgery and sepsis in newborns caused no further reduction in actin polymerisation. Changes in PMN shape after stimulation with FMLP were reduced in the newborns. PMN chemotaxis was significantly lower in healthy newborns than in adults (17 +/- 4 microns v 24 +/- 5 microns; P < .0001) and was even lower in septic newborns (11 +/- 4 microns; P < .005). Surgery and anaesthesia did not alter chemotaxis.