Clinical use of laser angioplasty is limited by the lack of an adequate guidance system. As a first step toward developing a reliable guidance system, laser-induced surface fluorescence and a fluorescent probe were used to differentiate plaque from normal arterial wall. The aortas from four normal New Zealand white rabbits and six atherosclerotic rabbits were studied in vitro. Rabbits from each group received 2.5 mg/kg of hematoporphyrin derivative intravenously 24 hours before death. Segments of the aortas were irradiated with a helium-cadmium laser, and the tissue surface fluorescence spectra were recorded with an optical multichannel analyzer. A plaque index, based on the resulting spectra, was calculated for each specimen of aorta. The spectra from normal aorta without hematoporphyrin derivative, normal aorta with hematoporphyrin derivative, and from plaque of atherosclerotic rabbits without hematoporphyrin derivative showed the same wavelength dependence. The plaque index values were not significantly different from one another. However, in plaque from atherosclerotic rabbits given hematoporphyrin derivative, the spectrum was markedly different, showing a broad spectral peak at 632 nm. This spectral peak corresponds to the spectral peak of hematoporphyrin derivative and was only seen in the plaque of atherosclerotic rabbits given hematoporphyrin derivative. The plaque index for these specimens was significantly different from all other specimens (p < 0.001). This difference in fluorescence spectra and plaque index could be incorporated into a guidance system for laser angioplasty. © 1988.