Murine melanoma cells were engineered to express interleukin-2 (IL-2), interferon-gamma (IFN-gamma) or both cytokines at various dose levels by means of the adenovirus-enhanced transferrinfection (AVET) method. The gene-modified cells were tested for their potency to induce an antitumor immune response in two experimental settings with different tumor load. In a prophylactic vaccination model, both IL-2 and IFN-gamma showed a dose-dependent protection against tumor cell challenge in two melanoma models. In the therapeutic vaccination model, where mice with measurable tumors were treated, immunization with IL-2 or IFN-gamma gene-modified cells led to complete tumor regression in 30% or 20% of the tumor-bearing animals respectively. The combination of IL-2 + IFN-gamma resulted in complete tumor regression in up to 50% of the tumor-bearing mice.