Selective depletion or inactivation of specific myeloid populations (neutrophils, macrophages) and lymphoid populations (helper T cells, cytolytic T cells) in EMT6 sarcoma-bearing mice was used to determine the contribution of each of these host immune cell types to the curative outcome of Photofrin-based photodynamic therapy (PDT). Immunodepletion of neutrophils and cytolytic T cells initiated immediately after PDT resulted in a marked reduction in PDT-mediated tumor cures. Significant reduction in the cures of EMT6 tumors was also achieved by immunodepletion of helper T cells and inactivation of macrophages by silica treatment. The initial tumor ablation by PDT was not affected by any of the above depletion treatments. These results provide direct evidence that the contribution of neutrophils, macrophages and T lymphocytes is essential for the maintenance of long-term control of PDT-treated tumors.