The objective of this study was to characterize microbiological factors independently associated with higher mortality rates following nosocomial bloodstream infection. All patients admitted to the University of Iowa Hospitals and Clinics between 1 July 1989 and 30 June 1990 who developed a nosocomial bloodstream infection were included. The crude in-house mortality for the 364 patients with nosocomial bloodstream infections was 33%. These deaths accounted for 25% of all in-hospital deaths. Significant risk factors for death from bloodstream infection included diagnoses of cancers and diseases of the cardiovascular and respiratory systems (p < 0.01). Neither previous surgery nor neutropenia was associated with higher mortality rates. Whereas the crude mortality rates associated with gram-negative (33%) and gram-positive (31%) bloodstream infections were similar, that associated with fungemia was higher (54%, p < 0.02). The mortality associated with secondary bloodstream infections (46%) was higher than that associated with primary bloodstream infections (28%, p < 0.001). Furthermore, polymicrobial infections had a worse prognosis than infections from which a single pathogen was isolated (p < 0.05). A multivariate, logistic regression model identified four variables that independently predicted mortality (p = 0.025): age (OR 1.01 per year; CI95 1.00-1.02); cancer (OR 2.35, CI95 1.26-4.37) or diseases of the cardiovascular or respiratory systems (OR 2.20, CI95 1.04-4.67); polymicrobial infection (OR 2.34; CI95 1.21-4.53); and secondary bloodstream infection (OR 2.46; CI95 1.50-4.02). The last variable was the strongest independent predictor. Our study demonstrates the importance of microbiological factors in the outcome of nosocomial bloodstream infections.