The expression of the Bcl-2 oncoprotein was studied in pre-treatment bone-marrow samples from 63 patients with multiple myeloma, using an immunohistochemistry technique. A variable expression of the Bcl-2 protein was found in myeloma cells. 43% of the patients had strong expression of the Bcl-2 protein in the malignant cells. Forty patients received alpha-interferon, whereas 23 patients received melphalan/prednisone therapy. A significant association (p = 0.012) was found between high levels of Bcl-2 expression in myeloma cells and resistance to interferon therapy. No such correlation was found in the melphalan/prednisone treated patients. The data indicate that over-expression of Bcl-2 may be a cause for resistance to interferon therapy in myeloma and that staining for Bcl-2 expression in myeloma cells may have a predictive value for this treatment.