Three potential guidance mechanisms for pulsed laser angioplasty were tested for their ability to discriminate between different tissue types. Holmium:YAG laser energy (wavelength=2.1 um, 100 mJ/pulse, 12.7 J/mm2 fluence) was delivered through a 100 um fiber into normal artery, fibrous plaque, and calcified plaque, as well as saline and blood. Plasma emission, mechanical fiber recoil, and acoustic shock wave were all measured during laser irradiation of these different substances. Plasma emission was detected by a photodiode at the proximal end of the fiber. Mechanical fiber recoil was detected using a phono cartridge mechanically coupled to the fiber 60 cm from the distal end. Acoustic sound waves were detected with a hydrophone in close proximity to the target site. The probability of generating plasma emission and the relative magnitudes (1-4) of the mechanical recoil and acoustic signal are as follows: Signal Blood Normal Aorta White Plaque Calcified Plaque plasma 0% 0% 0% 99% acoustic 4 1 1 4 recoil 1 2 2.5 4 A Fourier transform of the acoustic signal showed differences between blood, normal artery or non-calcified plaque, and calcified plaque. Mechanical recoil does not provide additional information. These techniques do not differentiate normal tissue from fibrous plaque but will discriminate calcified plaque from blood, normal artery, and non-calcified plaque. These techniques are relatively easy to implement and provide potentially useful feedback to guide laser ablation. Conclusion: The presence of plasma is a good indicator of calcified plaque; when used in conjunction with the acoustic signal it could indicate whether the fiber catheter is on calcified plaque, non-calcified tissue, or in blood.