The purpose of this study was to investigate coronary endothelial dysfunction in young healthy smokers by measuring myocardial blood flow (MBF) using [(15)O]H(2)O-PET. The study population was 18 young male volunteers consisted of 9 smokers (age: 23.8+/-1.1yr) and 9 non-smokers (age: 25.0+/-2.5yr). The smokers had been smoking cigarettes for 6.6+/-2.5 pack years. Myocardial [(15)O]H(2)O-PET was performed at rest, during cold (5 degrees C) pressor stimulation and during adenosine infusion. Left ventricular (LV) input function and tissue time-activity curves were obtained by drawing region of interest (ROI) on the LV blood pool and myocardium images obtained by non-negative matrix factorization (NMF) of dynamic [(15)O]H(2)O-PET data, and MBF was calculated using these time-activity curves and single compartmental model. There were no significant difference in resting MBF between two groups (smokers: 1.43+/-0.41 and non-smokers: 1.37+/-0.41ml/g/min; P=NS). However, during cold pressor stimulation, MBF in smokers was significantly lower than that in non-smokers (1.25+/-0.33 vs. 1.59+/-0.29ml/g/min; P=0.019). MBF changed to 90+/-24% of resting MBF in smokers and 122+/-28% in non-smokers. The difference in the ratio of cold pressor MBF to basal MBF between two groups was also significant (P=0.024). During adenosine infusion, however, hyperemic MBF did not differ significantly between smokers and non-smokers (5.81+/-1.99 vs. 5.03+/-1.27ml/g/min; P=NS). This study shows that [(15)O]H(2)O PET analysis can reveal that endothelial dysfunction occurs in even young smokers of about 6 pack years.