Following treatment of Lewis lung carcinomas (LLC) by Photofrin-mediated photodynamic therapy (PDT), tumor tissues and sera of host mice were collected for the analysis of complement activity. Elevated tumor C3 levels were detected between 1 and 24 h after PDT, while serum C3 levels increased significantly at 24 h post therapy. Increased alternative complement pathway activity in the serum was evident between 1 and 3 days post PDT. Blocking C3a- or C5a-receptors in the host mice decreased the efficacy of PDT in producing LLC tumor cures, supporting the importance of complement action in PDT-mediated tumor destruction.