Peritoneal macrophages treated in vivo with haematoporphyrin derivative (HPD) exhibited significant enhancement of Fc receptor mediated ingestion activity. To examine this process more rigorously, we studied photodynamic activation of macrophages by exposure in vitro of mouse peritoneal cell cultures (containing macrophages and B and T-lymphocytes) to HPD and red fluorescent light. A short (10 s) exposure of peritoneal cells in medium containing 0.03 ng HPD/ml produced the maximal level of ingestion activity of macrophages. A singlet oxygen quencher, DABCO, inhibited the effect of HPD. Photodynamic treatment of macrophages alone did not activate the cells and activation was only observed when macrophages were mixed with photodynamically treated non-adherent cells (B and T-lymphocytes). These results imply that activation of macrophage is a consequence of peroxidation of lymphocyte membrane lipids by photodynamically generated singlet oxygen.