Coagulase-negative staphylococcal septicemia is the most prominent nosocomial infection in neonatal intensive care units. Immaturity of host defenses in premature neonates is assumed to constitute an important risk factor. Opsonophagocytosis is considered to be the key host defense system against staphylococci with IgG antibodies as a major opsonin. For this reason we have studied serum IgG antibody titers and opsonic activity to coagulase-negative staphylococci in 20 infants with septicemia and 40 matched control subjects. In addition, we assessed the effect of administration of fresh frozen plasma (FFP) on IgG antibody titer and serum opsonic activity in 12 patients with septicemia. IgG antibodies, quantified by ELISA and opsonic activity, determined by flow cytometry, were expressed as a percentage of the value of pooled normal human reference serum. Both patients and control subjects showed low IgG titers (median, 21%; range, 1-192%) and a low opsonic activity (median, 33%; range, 8-484%) at birth. During the first 2 postnatal wk IgG titers decreased significantly in septicemia patients (from a median of 30 to 17%, p = 0.025), but not in control subjects, whereas opsonic activity remained unchanged. The titer of IgG antibodies increased significantly in septicemia patients after FFP administration (from a median of 17 to 41%, p = 0.002), whereas the effect on opsonic activity was unpredictable, showing a moderate increase in 10 out of 12 infants, and in 2 patients even a substantial decrease (>50%), despite adequate opsonic activity in the corresponding FFP batches. Immunoblotting of sepsis isolates with the corresponding patient sera demonstrated that septicemic infants may generate IgG antibodies against their blood isolate. Neonates who acquire coagulase-negative staphylococcal septicemia cannot be distinguished from control subjects on the basis of IgG antibodies and opsonic activity to staphylococci either at birth or during the first 2 postnatal wk. The administration of FFP to septicemia neonates has an unpredictable effect on opsonic activity and therefore does not seem to be a useful addition to antibiotic therapy.