Antibody and complement are essential to host defense against infection with coagulase-negative staphylococci in the neonate. To evaluate the influence of antibody on C3 deposition, we compared the C3 fragments deposited on coagulase-negative staphylococci after opsonization with normal human serum or with hypogammaglobulinemic serum. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot (immunoblot) analysis, the degradation products of C3 were less apparent at 1 and 2 min after opsonization with hypo- and agammaglobulinemic serum than those from normal human serum. This finding suggested that antibody contained in normal human serum contributes to efficient C3 deposition in the early phases of opsonization. There was no clear difference in C3 deposition when slime-producing strains were compared with non-slime-producing strains. The addition of intravenous immunoglobulin to hypogammaglobulinemic serum and serum from premature neonates rendered C3 deposition comparable to that seen with normal human serum. The data from these experiments suggest that the addition of immunoglobulin G may improve host defense against coagulase-negative staphylococci in the hypogammaglobulinemic premature neonate by enhancing C3 deposition, thus promoting opsonophagocytosis of these bacteria.