The co-culture of mouse peritoneal macrophages and Lewis lung carcinoma cells induces the relase of a metal-dependent type IV collagen-degrading proteinase which is not produced in detactable amounts by either cell type cultivated alone. Conditioned media of the co-cultures degrade both pepsin-extracted type IV collagen from human placenta and mouse type IV procollagen. Thus macrophages can interact with tumor cells to degrade basement membrane type IV collagen: this might be of importance to allow cancer invasion and metastasis.