The causes of death were investigated in 315 adults with acute leukemia during a 7-year period (1966-1972). Infection alone or in combination was the most common cause (75%), followed by hemorrhage (24%) and organ failure (9%). Most of the infections were either systemic or pulmonary. Seventy-five percent of the systemic infections and 72% of the pneumonias were caused by bacteria. Klebsiella pneumoniae, Escherichia coli and Pseudomonas aeruginosa were the most frequent organisms isolated. After 1968, there was a sharp decrease in the number of fatal infections caused by Pseudomonas aeruginosa and a marked increase in the incidence of fatal infections caused by Klebsiella spp. and E. coli. Infections caused by Gram-positive cocci occurred in only 3% of the cases. The incidence of systemic fungal infections was 13%; most common fungi causing infection were Candida spp. and Aspergillus spp. Eighty-five percent of 159 patients with a terminal neutrophil count of less than 100/mm3 died of infection, compared to 48% of 62 patients with a terminal neutrophil count of greater than 1000/mm3. Hemorrhage was mostly due to thrombocytopenia (61%) and disseminated intravascular coagulation (12%). This study indicates that infection continues to be the most common cause of death in patients with acute leukemia. Although advances in antibiotic therapy have changed the distribution of causative organisms, ultimate control of infection requires further improvements in supportive care measures which rectify impairments in the patients' host defense mechanisms.