It has recently been proposed that photosensitized erythrocytes may play an important role in the delivery and targeting of agents such as photosensitizers and chemotherapeutics for use in cancer treatment. It has been suggested that loading of photosensitized erythrocytes with chemotherapeutic agents would provide an ideal means of combining both treatment modalities. The recent application of real-time confocal laser scanning microscopy to the study of immediate effects of photodynamic activation on photosensitized erythrocytes has enabled us, in this study, to distinguish between the differential susceptibility of age-density resolved sub-populations of human erythrocytes to photodynamic activation. In this study we demonstrate that younger (low age-density) sub-populations of photosensitized erythrocytes are less susceptible than older (high age-density) sub-populations to photodynamic activation. We also demonstrate that this phenomenon is exhibited by cells photosensitized using hematoporphyrin derivative and rose bengal as photosensitizers. In both cases no significant difference in uptake of photosensitizer by both populations could be observed using absorbance spectrophotometry. The study suggests that age-density resolution of erythrocytes prior to loading and photosensitization might provide a means of enhancing the release of loaded components from the photosensitized system and this would, in turn, enhance the potential use of photosensitized erythrocytes as delivery or targeting systems for use in combination cancer therapies. (C) 1997 Elsevier Science Ireland Ltd.