OBJECTIVE To evaluate the radiologic and follow-up features of multilocular thymic cysts in children with human immunodeficiency virus (HIV) infection. METHODS Four HIV-infected children with large anterior mediastinal masses depicted at routine chest radiography underwent ultrasonography (US), unenhanced and contrast material-enhanced computed tomography (CT), and unenhanced and gadolinium-enhanced MR imaging of the chest. Gallium scanning was also performed in three of the four children. The patients underwent follow-up radiologic examinations for 8-15 months. RESULTS The multiloculated nature of the masses was depicted at contrast-enhanced but not unenhanced CT. Similarly, the septations were depicted on T2-weighted, short inversion time inversion-recovery (STIR), and contrast-enhanced T1-weighted, MR images but not on the unenhanced T1-weighted images. US scans depicted the septations within each mass, but findings were technically limited because only portions of each mass were depicted. Gallium scans in three masses depicted uptake of radionuclide in two and no uptake in one. Surgical biopsy was performed in each mass: Follicular hyperplasia and diffuse plasmacytosis of the thymus were found but not evidence of neoplastic or infectious origin. At follow-up, the mass decreased in volume in two patients, did not change in one patient, and increased in volume in one patient. CONCLUSIONS HIV-infected patients with asymptomatic mediastinal masses depicted at routine chest radiography should undergo contrast-enhanced CT. If a solid mass is depicted, biopsy should be performed to exclude neoplastic or infectious origins. If a multiloculated anterior mediastinal mass is depicted, symptomatic follow-up is adequate since the finding represents a rare multilocular thymic cyst that does not have negative clinical implications.