In a prospective cohort study of 70 consecutive, asymptomatic human immunodeficiency virus type 1 (HIV-1)-infected adults, splenomegaly was found by physical examination in 23% of patients and by ultrasound in 66%. Patients with concomitant liver disease had a higher prevalence of splenomegaly (RR 1.84; P<.001). During a 1-year follow-up of 66 patients, splenomegaly at enrollment was not predictive of any clinical event, and splenomegaly was not associated with a higher risk of developing AIDS during a median follow-up of 6.1 years.