To assess the clinical significance of splenic tuberculosis in patients infected with human immunodeficiency virus (HIV) type 1, we compared 20 patients who had splenic tuberculosis with 20 randomly selected, HIV-infected patients with culture-proven tuberculosis for whom splenic involvement had been ruled out by ultrasonography. All of the patients were male prison inmates and intravenous drug users. Statistically significant differences (P < .05) were detected between patients with splenic involvement (median CD4+ cell count, 54/mm3) and those without splenic involvement (median CD4+ cell count, 92/mm3). No specific symptoms suggesting splenic involvement were detected in the patients with splenic tuberculosis. All patients received antituberculous drugs, and none of these patients required splenectomy. The median survival was similar in both groups. Splenic tuberculosis occurs in more-severely immunocompromised HIV-infected patients, the prognosis is generally good, the clinical response to therapy is usually favorable, and splenectomy is rarely necessary.