The human T-lymphotropic virus type III (HTLV-III) is the primary etiologic agent of the acquired immunodeficiency syndrome (AIDS). HTLV-III infection in patients with prior underlying immune deficiency states such as cancer has not yet been studied. We report on the occurrence of clinically atypical opportunistic infections in previously immunocompromised patients that resulted from transfusion-acquired HTLV-III infection. Development of unusual infectious diseases in patients with neoplasms and other underlying immune deficiency disorders should lead to consideration of HTLV-III infection. Surveillance data should be obtained on these patients to accurately define the scope of HTLV-III infection.