Malignant melanoma is a prime example of cancers that respond poorly to various treatment modalities including chemotherapy¹. A number of chemotherapeutic agents have been shown recently to act by inducing apoptosis, a type of cell death antagonized by the bcl-2 gene². Human melanoma expresses Bcl-2 in up to 90% of all cases^3–7. In the present study we demonstrate that bcl-2 antisense oligonucleotide treatment improves the chemo-sensitivity of human melanoma grown in severe combined im-munodeficient (SCID) mice. Our findings suggest that reduction of Bcl-2 in melanoma, and possibly also in a variety of other tumors, may be a novel and rational approach to improve chemosensitivity and treatment outcome.