6 patients with cutaneous malignant melanoma and multiple secondary cutaneous lesions were treated with intralesional methanol extraction residue of bacillus Calmette Guerin (MER-BCG). Separate lesions were injected with purified protein derivatives (PPD) in 5 of the study patients. 5 of the 6 MER-BCG injection lesions developed marked inflammation clinically. Excisional biopsy 7-14 days later demonstrated complete dissolution of tumor in 2 patients and was accompanied by infiltration with acute and chronic inflammatory cells; 3 lesions revealed necrosis with residual tumor, and in 1 patient there was no apparent host response. Clinical tumor regression was not observed with PPD applied intralesionally, although histopathologic analysis revealed a granulomatous inflammatory response in 3 of 5 patients. No patient demonstrated regression of uninjected cutaneous lesions (4 evaluable patients) or visceral lesions (2 patients). The critical determinants of tumor regression are the size, site and depth of the lesion in relationship to the cutaneous surface. The mechanism of tumor eradication may be related to 'innocent bystander' necrosis secondary to nonspecific inflammation rather than immunologically mediated via host sensitization.