Carbon-10-labeled carbon dioxide ((10)CO2) with a half-life of 19.3 seconds offers almost ideal characteristics as a positron emission tomography (PET) tracer for assessment of the regional cerebral blood flow (rCBF) distribution, enabling multiple independent measurements at short intervals. To appraise the feasibility of (10)CO2 for localizing and characterizing human brain function in single subjects, the authors chose a well-characterized activation paradigm. In 6 healthy volunteers, 50 to 64 independent PET scans of the rCBF distribution were acquired while viewing an annular reversing checkerboard presented at 10 reversal frequencies between 0.03 and 30 Hz. Changes in regional cerebral activity as a function of reversal frequency were modeled in every subject using a set of polynomial basis functions, which, as predicted, showed highly significant second or third order relations located in the striatal cortex. Correlation coefficients (R2) ranged from 0.46 to 0.63. The average intersubject maximal response relative to the 0.03 Hz condition was 8.0% +/- 1.7% SD occurring at stimulus contrast reversal frequencies between 6 and 15 Hz with an average of 11.8 +/- 3.8 (SD) Hz. From the qualitative and quantitative replication of previous results it is concluded that (10)CO2 PET is a feasible technique for human brain mapping studies and a great improvement compared with the existing oxygen-15-labeled water (H(2)(15)O) PET method, particularly for single subject studies and parametric design.