Polymicrobial bacteremia increased from 6% in 1970 to 13% in 1975 in patients with bloodstream infections. This type of serious infection most commonly complicated genitourinary (27%) and gastrointestinal (26%) conditions, frequently followed invasive procedures (68%), was more common in hospitalized patients (73%), and was often associated with malignancies (25%) or immunosuppressive or cancer chemotherapy (34%). Although polymicrobial endocarditis was more commonly encountered in recent years, this infection accounted for only 4.5% of patients with multiple organism bacteremias. Gram-negative aerobic bacteria were isolated from 62% and anaerobic bacteria in 39% of patients with polymicrobial bacteremia compared with 37% and 14%, respectively, in patients with monomicrobial bacteremia. In the 88 patients with polymicrobial bacteremia, the mortality was 44.5%, compared with 18.0% in patients with monomicrobial bacteremia.