Background and Objective: Laser-induced fluorescence spectroscopy (LIFS) may be capable of guiding laser angioplasty by discriminating normal and atherosclerotic artery and by determining catheter-tissue environment. Previous optical multichannel analyzer based LIFS systems have been expensive and cumbersome. To simplify LIFS, a system based on photomultiplier tubes was developed and evaluated. Study DesignfMateriaZs and Methods: Tissue fluorescence was induced by a helium cadmium laser (wavelength = 325 nm, power = 0.24.5 mW), collected by clinical multifiber laser angioplasty catheters and directed through one of two filters (10 nm bandpass, 380 nm or 440 nm peak transmission) to a photomultiplier tube. An LIFS ratio was defined as the relative intensity at 380440 nm after calibration with an elastin fluorescence spectrum; 157 coronary artery cadaveric specimens were evaluated spectroscopically and histologically. To evaluate the utility of LIFS to optimize catheter position by determining catheter-tissue contact, by determining saline dilution of blood, and by orienting eccentric multifiber catheters a new variable, the total fluorescence intensity (TFI) was defined as the sum of arterial fluorescence intensities at 380 nm and 440 nm. TFI was recorded in vitro through multifiber catheters from 20 arterial specimens in vitro in blood and evaluated as a function of the catheter-totissue distance (d) over a range from 0 to 400 p. Results: Defining normal specimens as those with an intimal thickness 5200 p, and atherosclerotic as those with an intimal thickness >200 p, 47/50 (94%) normal and 85/107 (79%) atherosclerotic specimens were correctly classified using a threshold LIFS ratio of 2.0. Mean (&SE) normal ratio was 1.76-CO.02 and mean atherosclerotic ratio was 2.78 f 0.08 (P I 0.01). The classification accuracy of atherosclerotic specimens increased with intimal thickness so that 95% of atherosclerotic specimens (69/73) with intimal thickness 1400 p were correctly classified. TFI was capable of determining catheter-tissue contact as maximal TFI was recorded with the catheter in contact with the tissue (d = 0 p) and decreased markedly with distance (to 52 k 6% at d = 100 p, 19 2 4% at d = 200 p, and 3 f 1% at d = 300 p). TFI was recorded from ten arterial specimens in bloodhaline mixtures ranging in hematocrit from 0% (saline) to 50% (whole blood). TFI was capable of detecting saline hemodilution of blood as TFI decreased mark-