A method for the in vivo determination of cerebral blood volume was tested in 15 adult rhesus monkeys. The technique utilized external residue detection and required the serial measurement of two mean transit times, namely, that of an intravascular tracer, C15O hemoglobin, and that of a diffusible tracer, H215O. In computing the mean transit time for the intravascular tracer, the conventional Hamilton extrapolation of the downslope of the recording obtained for the washout of the tracer from the brain subsequent to an intracarotid bolus injection was found to be inadequate, yielding a mean transit time that systematically underestimated that parameter. Alternatively, the use of a power law extrapolation, as proposed by Huang, allowed a more accurate prediction of the vascular mean transit time. The preliminary studies testing the method predicted that the relationship between cerebral blood volume (CBV) and cerebral blood flow (CBF) was adequately represented by the equation CBV = 0.80CBF0.38, with a correlation coefficient of r = 0.90 for the cerebral blood flow range of 16 to 134 ml/100 g min-1 with a normocapnic cerebral blood volume of 3.5 ml/100 g perfused brain tissue (arterial PCO2 = 37 torr, CBF = 50 ml/100 g min-1.