The objective of this study is to determine the effect of short-term (3 weeks) and long-term (10 weeks) cigarette smoking on the transarterial wall oxygen gradient. Female New Zealand White Rabbits (3-4 kg) were exposed to the smoke of seven nonfiltered cigarettes daily and their transarterial wall oxygen gradients measured at 3 weeks or 10 weeks before and during cigarette smoke exposure. Arterial blood oxygen content, percent of carboxyhemoglobin, and arterial blood pressure were recorded during the experiments. Short-term cigarette smoking resulted in a decrease in the artery wall oxygen content only during exposure to cigarette smoke that corresponded to arterial blood hypoxia. Long-term cigarette smoke exposure resulted in a sustained decrease in artery wall oxygen content noted 24 hours after last exposure to cigarette smoke with normal levels of arterial blood oxygen and an acute decrease during cigarette smoke exposure with corresponding arterial blood hypoxia. These results were noted despite no differences in blood pressure or evidence of atherosclerotic lesions. Short-term cigarette smoking results in artery wall hypoxia only during cigarette smoke exposure and arterial blood hypoxia while long-term cigarette smoking results in sustained artery wall hypoxia in the presence of normal arterial blood oxygen content.