An active specific immunotherapy trial has been implemented in patients with malignant melanoma utilizing the mouse anti-id MAb MK2-23. The latter bears the internal image of the determinant by the anti-HMW-MAA MAb 763.74. The immunogenicity of anti-id MAb MK2-23 is enhanced by conjugation to a carrier and administration with an adjuvant. Anti-id MAb MK2-23 induced humoral anti-HMW-MAA immunity in about 60% of the immunized patients. The latter was associated with a statistically significant survival prolongation. It is suggested that anti-HMW-MAA immunity may have a beneficial effect on the clinical course of the disease by inhibiting the function of HMW-MAA in the biology of melanoma cells.