The present study was undertaken to determine if measurement and analysis of phagocyte function are useful for diagnosis and staging of infection. Circulating phagocyte activity was measured in healthy volunteers and sequentially in patients with acute infections of different types and severity, including those with diabetes mellitus or human immunodeficiency virus (HIV) infection. Using an automated luminescence system, these phagocyte functions were measured in whole blood: basal and phorbol 12-myristate 13-acetate (PMA)-stimulated oxidase activity, basal and PMA-stimulated simple dioxygenation (e.g., oxidase-driven haloperoxidase activity), and circulating and primed opsonin receptor-dependent dioxygenation. Multiple discriminant analysis of these data showed significant differences between healthy controls, diabetic patients, HIV-positive subjects, and patients with pneumonia or sepsis syndromes. Longitudinally, circulating phagocyte function correlated with clinical condition, severity of infection, and outcome. This methodology provides rapid, objective, and sensitive diagnostic and monitoring information for patients with infections.