To assess the most relevant features of hospital-acquired pneumococcal bacteremia, all cases of pneumococcal bacteremia at a single teaching hospital that occurred during 1988-2000 were prospectively studied. During this period, 374 cases of pneumococcal bacteremia were documented; 39 (10%) of these episodes were hospital acquired. Twenty-nine (74%) cases occurred during the period of December through May. Eleven (28%) of 39 patients had received antimicrobial agents in the month before the onset of bacteremia. All patients had underlying diseases that predisposed them to pneumococcal infection. The most common origin of infection was the respiratory tract, followed by the intra-abdominal region. Fifteen strains were fully susceptible to penicillin, and 20 were intermediately resistant. Only 25 strains were susceptible to erythromycin; all strains that were resistant to erythromycin were penicillin nonsusceptible. Eighteen (46%) of 39 patients died; the mortality rate related to infection was 39%.