Three tumor antigens, TAG-72, carcinoembryonic antigen and a 90 Kd antigen, recognized by monoclonal antibodies (MAbs) B72.3, B1.1 and B6.2, respectively, are differentially expressed on the surface of four human breast carcinoma cell lines. These cell lines, MCF-7, BT-20, MDA-MB-231 and ZR-75-1, also expressed normal surface antigens such as the class I major histocompatibility and a second antigen found on the surface of all human cells by the binding of MAb B139. Treatment of these cells with human recombinant clone A leukocyte interferon (IFN-aA) usually resulted in an enhanced expression of the surface antigens constitutively expressed. For example, the level of B6.2 reactivity to the surface of the ZR-75-1 cells was increased more than 3-fold following IFN-aA treatment. In contrast, ZR-75-1, BT-20 and MD-MB-231 were all negative for the TAG-72 antigen both before and after IFN-aA treatment. The IFN-aA induced tumor antigen expression on the MCF-7 cell surface was shown to be time and dose dependent and consisted of a heterogeneous population of cells that exhibit clonal diversity in their response to tumor augmentation by IFN-aA. The diversity among the MCF-7 clones could not be explained by differences in the surface IFN-aA receptor.