The hypothesis for this research is that only in some brain areas, regional cerebral blood flow (rCBF) after tobacco smoking is correlated with arterial plasma nicotine concentrations. Twenty-one healthy adult tobacco smokers of both genders were studied after overnight tobacco abstinence. H(2)15O water was used to measure rCBF. Six separate scans were taken about 12 min apart with the subjects' eyes closed and relaxed. Research tobacco cigarettes smoked were of average (1.0 mg) and low (0.08 mg) nicotine but similar tar yield (9.5 and 9.1 mg). Increases in normalized rCBF were obtained in the occipital cortex, cerebellum, and thalamus, and decreases in the anterior cingulate, nucleus accumbens, amygdala, and hippocampus immediately after smoking the first average nicotine yield cigarette of the morning. After smoking the second average nicotine yield cigarette, the effects were less than smoking the first. Low-nicotine cigarettes produced fewer changes in rCBF than those after the first average cigarette. As expected, statistically significant correlations were found between increases in arterial plasma nicotine and HR. Correlations with arterial nicotine on rCBF were statistically significant in brain areas with the greatest changes in relative blood flow such as the cerebellum and occipital cortex. Nicotine delivery by tobacco smoking is only one of the factors, which contribute to changes in rCBF.