The influence of the severity of pneumonia and comorbidity factors, as predictors of clinical outcome, was assessed in patients with microbiologically documented pneumococcal bacteremic pneumonia treated with penicillin or third generation cephalosporin monotherapy in a 5-year retrospective study. Among 288 patients admitted to three Spanish hospitals with bacteremic pneumococcal pneumonia, 65 (23%) were included. Twenty-four were treated with penicillins and 41 with a third-generation cephalosporin. Twenty-seven patients (42%) had severe pneumonia and 41 (63%) had a comorbidity index >1. Twenty-one patients (32%) were infected with penicillin-resistant strains. Four cases (2 with penicillin-resistant strains; 3 treated with cephalosporins) were clinical failures. Four cases (3 with penicillin-resistant strains; 2 treated with cephalosporins) died, i.e. 6% mortality rate. The only factor that influenced empirical treatment election was HIV-positive condition. Clinical outcome was not influenced by treatment election, penicillin susceptibility of the infecting pneumococci, patient basal conditions or severity of pneumonia, but the latter was associated with mortality and length of hospitalization.