We reviewed the clinical course of 245 adults who underwent splenectomy for trauma to assess the risk of both early and late serious infection. Twenty-one patients (9%) had an early serious infection (sepsis) during hospitalization for splenectomy. The mortality rate was 62% in patients with early sepsis, and encapsulated bacteria were isolated from the blood of 43% of patients with sepsis. Only one of 58 patients with isolated splenic injury had sepsis (2%), and the risk of early sepsis increased when three or more concomitant injuries were present (p less than 0.05). Stepwise multiple regression analysis revealed that patients with injuries to the pancreas, colon, or central nervous system or with extremity fractures had an increased risk of sepsis (p less than 0.05). The risk of sepsis was not influenced by age, the type of injury, delay in operation, use of drains, or other individual injuries. Sufficient information was available to assess the risk of late serious infection for 140 surviving patients (63%). Follow-up ranged from 2 to 277 months. Three late infections occurred at 2, 8, and 15 years after splenectomy; two were due to Streptococcus pneumoniae. None of these patients died. There were no identifiable factors influencing the risk of late infection. These results suggest that the risk of early serious infection in adults after splenectomy for trauma is low when isolated splenic injury is present but that this risk is increased by both the degree of injury and the presence of certain associated injuries. Encapsulated bacteria are frequent pathogens in both early and late infections. The mortality rate related to an early septic episode is high, but the risk of late serious infection is low and is not related to identifiable factors that decrease host defenses.