In 1996, we showed that inflamed atherosclerotic plaques give off more heat and that vulnerable plaques may be detected by measuring their temperature. Plaque temperature is correlated directly with inflammatory cell density and inversely with the distance of the cell clusters from the luminal surface. It is inversely related to the density of the smooth muscle cells. We found no significant association between temperature heterogeneity and presence of Chlamydia pneumoniae in plaque or the gross color of human atherosclerotic carotid plaques. We also found pH heterogeneity in plaques from human carotid artery and aortas of Watanabe atherosclerotic rabbits and apolipoprotein E-deficient mice. Areas with lower pH had higher temperature, and areas with a large lipid core showed lower pH with higher temperature, whereas calcified regions had lower temperature and higher pH. We also developed a thermography basket catheter and showed in vivo temperature heterogeneity in atherosclerotic lesions of atherosclerotic dogs and Watanabe rabbits. Thermal heterogeneity was later documented in human atherosclerotic coronary arteries. Temperature difference between atherosclerotic plaque and healthy vessel wall is related to clinical instability. It is correlated with systemic markers of inflammation and is a strong predictor of adverse cardiac events after percutaneous interventions. Thermography is the first in a series of novel "functional" imaging methods and is moving to clinical trials. It may be useful for a variety of clinical and research purposes, such as detection of vulnerable plaques and risk stratification of vulnerable patients.