Multiparameter flow cytometric analyses of polymorphonuclear neutrophilic granulocyte (PMNL) functions have been performed longitudinally in ten patients with large burns. The percentage of phagocytosing PMNLs was increased at admission (within 24 hours after injury) and through the first 10 days of hospitalization. The surface binding capacity and the ingestion of Staphylococcus aureus by each PMNL was increased during the same time period, and at day 2 the number of S. aureus ingested per patient PMNL was 35% higher than in the controls. The intracellular killing of Candida albicans was reduced by about 25% at admission. The microbicidal capacity was further compromised during the first 2 weeks after injury, with a reduction of intracellular killing of about 35% 5–10 days after admission. The kinetics of patient PMNL phagolysosomal acidification was altered during the first 20 days, as the initial alkalinization of the phagolysosomes documented in control PMNLs could not be demonstrated in PMNLs from patients with burns. In addition, measurements of maximal phagolysosomal acidification showed a lower pH in patient phagolysosomes than in the controls during the first 5 days. The patient PMNL H2O2 production was reduced at admission and through the first 10 days, with an oxidative burst that was 46% lower than the controls at day 5. The intracellular degradation of S. aureus proteins and DNA was slightly but significantly reduced at day 5 and day 10 after admission. The impairment of PMNL microbicidal capacity correlated with total body surface area burn. Patients ≥ 40 years and patients having inhalation injury showed a lower phagocytosis and a more impaired intracellular killing than patients <40 years and patients without inhalation injury. The results indicate an activation of PMNLs in the early phase after thermal injury, which is followed by impairment of PMNL functions that may predispose to infectious complications.