Intracoronary Raman spectroscopy could open new avenues for the study and management of coronary artery disease due to its potential to measure the chemical and molecular composition of coronary atherosclerotic lesions. We have fabricated and tested a 1.5-mm-diameter (4.5 Fr) Raman catheter capable of collecting Raman spectra in both the fingerprint (400-1800 cm(-1)) and high-wavenumber (2400-3800 cm(-1)) regions. Spectra were acquired in vivo, using a human-swine xenograft model, in which diseased human coronary arteries are grafted onto a living swine heart, replicating the disease and dynamic environment of the human circulatory system, including pulsatile flow and motion. Results show that distinct spectral differences, corresponding to the morphology and chemical composition of the artery wall, can be identified by intracoronary Raman spectroscopy in vivo.