Magnetic resonance (MR) images and neuropsychological testing data of 69 carbon monoxide (CO) poisoned patients were prospectively obtained within 1 day of CO poisoning, two weeks and six months. CO patients' Day 1 cross-sectional fornix surface area measurements, corrected for head size by using a fornix-to-brain ratio (FBR), were compared to normal age and gender-matched controls. Additionally, a within-subjects analysis was performed comparing the mean areas between CO patients' Day 1, 2 weeks and 6-month FBR. The FBR was correlated with patients' neuropsychological data. There were no significant differences between CO patients' Day 1 fornix measurements compared to normal control subjects. However, significant atrophic changes in the fornix of CO poisoned patients occurred at two weeks with no progressive atrophy at 6 months. By 6 months, CO patients showed significant decline on tests of verbal memory (when practice effects were taken into account), whereas visual memory, processing speed and attention/concentration did not decline. This study indicates that CO results in brain damage and cognitive impairments in the absence of lesions and other neuroanatomic markers.