No method has been reported for measuring CBF, repeatedly and noninvasively, in the rat brain. A new method is described, which is noninvasive to the brain, skull, or cervical large vessels. Two pairs of coincidence detectors were positioned, one over the rat brain and the other at the loop of a catheter inserted into the femoral artery. The coincidence head curve and arterial curve were recorded after intravenous injection of 1-[11C]butanol in 15 rats. CBF was calculated by one-compartment curve fitting ( CBFo ) from 1-min data and with the recirculation corrected height/area method from 3-min data ( CBFh X 3 min) and 5-min data ( CBFh X 5 min). CBFo agreed well with CBFh X 5 min, although a slight overestimation was observed in CBFh X 3 min. The normal CBFo in the normocapnic group (n = 6, paCO2 36.7 +/- 2.3 mm Hg) was 1.76 +/- 0.49 ml/g min (mean +/- SD). A good correlation was observed between CBFo (y) and PaCO2 (x), and the regression line was y = 0. 0629x -0.715 (r = 0.88, p less than 0.0001). We concluded that this method gives the stable blood flow values noninvasively and with a minimum loss of blood (less than 0.28 ml per measurement). Applications of this method include activation studies, studies on the effect of drugs and treatments, and water and oxygen extraction fraction studies using different tracers in the same rat.