Endothelial damage and platelet activation may mediate increased cardiovascular morbidity and mortality in tobacco cigarette smokers. Our study was designed to determine whether acute effects of tobacco smoking on endothelium and platelets could be avoided by the substitution of non-tobacco cigarettes. Twenty healthy nonsmokers smoked two tobacco cigarettes in 20 minutes and on another occasion (separated by 1 week) smoked two cigarettes made from wheat, cocoa, and citrus plants. Mean endothelial cell counts from venous blood before and after smoking tobacco cigarettes were 2.3 and 4.8 and before and after smoking non-tobacco cigarettes counts were 2.5 and 3.0. Mean platelet aggregate ratios before and after smoking tobacco cigarettes were 0.80 and 0.65 and before and after smoking non-tobacco cigarettes they were 0.81 and 0.78. Much greater effects of tobacco smoking on endothelial cell counts and platelet aggregate ratios suggest the possibility that non-tobacco cigarette smoking may be less harmful to the cardiovascular system than is tobacco cigarette smoking.