The demographic, clinical, pathogenetic, and microbiologic features of 185 consecutive patients with staphylococcal bacteremia recognized at Johns Hopkins Hospital from 1952 to 1965 are reviewed to isolate features responsible for and characteristic of staphylococcal sepsis. Bacteremia was commonest in the very young and very old. The overall mortality was 42%. A source of sepsis was usually found, with skin trauma and postoperative wound infection the commonest causes. Intravenous cutdowns and plastic catheters were significant sites for the origin of staphylococcal sepsis. Seventy-five percent of the patients studied had significant associated illnesses accompanying the bacteremia that adversely influenced the outcome. Arteriosclerotic cardiovascular disease, diabetes mellitus, and lymphoma-leukemia were present in many patients singly or in combination, and the role of associated illness in altering the host response to this infection is discussed. Twenty-five patients had Staphylococcus albus bacteremia, and although the characteristics of infection did not differ from S. aureus bacteremia, the mortality rate was 28%. Most staphylococci were phage typed. There were no strains associated with increased mortality, specific origin of sepsis, or type of associated illness.