Photodynamic therapy (PDT) of diseased tissues with hematoporphyrin derivative (HPD) within the cardiovascular system could be performed with a light-emitting antra-arterial optical fiber. However, the penetration of light at 631 nm through oxygenated whole blood first needs to be studied. In vitro studies were, therefore, performed to measure the transmission of 631 nm light, generated by an argon-ion pumped dye laser, through whole blood and serial dilutions of whole blood with the relatively translucent blood substitute Fluosol-DA. The results indicate that whole blood attenuates 631 nm light far greater than tissues, where HPD-PDT is currently applied, and that a 2 mm thickness of whole blood at a normal hematocrit may prevent a photodynamic tissue reaction when a conventional light dose is applied. Preliminary observations in rabbits treated in vivo with hematoporphyrin and 631 nm light via an intra-aortic optical fiber, with and without Fluosol-DA hemodilution, confirm these results. Hemodilution of whole blood with translucent liquids will enhance photodynamic tissue reactions and may be a necessary adjunct when this therapy is applied within the cardiovascular system.