In order to develop a reliable laser-induced fluorescence (LIF) guided laser angioplasty system, real time, pulse-by-pulse fluorescence spectra were recorded and the same fiberoptic was used for both detection of the fluorescence and for atheromatous tissue ablation. A 308 nm XeCl excimer laser served as the laser source for both the induction of fluorescence and the ablation. The fluorescence signal was induced at high laser energies during ablation without any serious change in the fluorescence pattern. A new characteristic fluorescence peak at 540 nm for atheromatous tissue was observed after treatment with chlortetracycline hydrochloride (CTC). This allowed the development of an algorithm and a subsequent index to discriminate the atheromatous tissue from the normal tissue. During atheromatous tissue ablation, this index changed as normal tissue was approached, thereby avoiding vessel perforation. Our results suggest that monitoring of this index through the catheter delivering the laser energy enhances selective ablation while simultaneously reducing the risk of vessel perforation.