The opsonic requirements of 65 strains of Staphylococcus epidermidis were compared in fresh and in heated normal human serum. The strains were isolated from patients with CAPD peritonitis (n = 26), neonatal septicaemia (n = 24) and nasal cultures (n = 15). A wide variation was observed in opsonic requirements between the different strains, both with fresh and with heated serum. Opsonization in heated serum proceeded less efficiently and higher concentrations (mean three-fold compared to fresh serum) were needed for adequate phagocytosis. However, a highly significant correlation was found between the minimal opsonic concentrations of fresh and of heated serum (r = 0.84, P less than 0.0005). In addition, S. epidermidis can become opsonized in agammaglobulinaemic serum. Thus, opsonization of S. epidermidis can be mediated by antibodies alone and by complement alone. Slime-producing strains and encapsulated strains did not require higher concentrations of serum to become opsonized. Opsonic requirements were highly significantly correlated with surface hydrophobicity. Enzymatic treatment rendered the strains more hydrophilic and decreased their opsonic requirements. Isolates from nasal cultures required significantly higher concentrations of both fresh and heated serum to become adequately phagocytozed, whereas isolates from CAPD peritonitis required higher concentrations of heated serum only compared to blood isolates. The uptake of S. epidermidis preopsonized in heated serum as determined in our direct phagocytosis assay did not result in a comparable chemiluminescence response.