Pneumococcal bacteremia is associated with a high morbidity and mortality, especially when leukopenia is present. To define further the possible factors associated with death in pneumococcal bacteremia, we reviewed all cases at 2 hospitals over a 1-yr period. Overall, increased mortality was associated with women (p = 0.009), nosocomial acquisition of the disease (p = 0.001), the presence of leukopenia (p = 0.00002) or thrombocytopenia (p = 0.025), shock (p = 4 X 10(-8)), and adult respiratory distress syndrome (p = 2 X 10(-7)). Leukopenic and nonleukopenic patients were compared further to ascertain factors that may predispose to leukopenia. Alcoholism was the only associated condition correlating with the presence of leukopenia (p = 0.036), and alcoholism and leukopenia occurred in a group of younger men. We conclude that the association of alcoholism, leukopenia, and pneumococcal sepsis is a distinct clinical entity seen in younger patients and is associated with a very high mortality.