To predict at an early phase the clinical course and outcome of nosocomial Staphylococcus aureus bacteremia, the APACHE II score at onset of bacteremia was calculated in 99 patients. A delta APACHE II score (i.e., the difference between this score and one calculated for the day before the bacteremia) was also determined. This delta APACHE II score was highly significantly correlated with clinical course (P<.001) and outcome (P<.001). The risk of a complicated clinical course and of dying from S. aureus bacteremia is determined at the very onset of bacteremia, and this risk can best be assessed by calculating the delta APACHE II score. Furthermore, a positive correlation was found between delta APACHE II scores and the level of serum opsonic activity (P=.003) toward S. aureus. Therefore, the complicated clinical course of S. aureus bacteremia is not due to a relative lack of specific opsonins.