Human serum and plasma have been demonstrated to enhance mortality in Staphylococcus aureus intraperitoneal infection in mice. Two different mechanisms seem to be involved. The effect of serum could be removed by adsorption to S. aureus protein A coupled to Sepharose 4 B and could be reconstituted by the addition of human IgG to IgG-depleted serum. Plasma diluted 1/10 in combination with purified fibrinogen also enhanced mouse mortality. Both effects could be demonstrated, when a coagulase-free variant of S. aureus was used. The results of viable counts of S. aureus in blood and peritoneum of the mice indicate that the enhancing effect of IgG alone and the enhancing effect of fibrinogen in combination with diluted plasma have different mechanisms.