Updated clin. outcome data are given on the transfer and expression of the granulocyte-macrophage colony stimulating factor (GM-CSF) cDNA and the cDNA of the reporter gene (β-galactosidase) to melanoma cells by direct intratumoral injection using vaccinia virus as a vector.Parameters assessed included toxicity, cytokine and passenger gene expression, anti-vaccinia immunity, and tumor regression.With 2× weekly injection, gene function was sustained over a protracted period despite the presence of anti-vaccinia immunity.Most often, injected metastases regressed and in some patients uninjected metastases regressed as well.Patients with only regional dermal metastases were placed into complete remission.Toxicity was minimal and limited to injection sites.