An overview of physical, physiological, and anatomical considerations focuses on air bubble and blood flow characteristics. This is followed by a description of a bench study that simulated the conditions covered in the hypothesis, using citrated pig blood. "Medline" was researched to find possibly undetected retrograde cerebral venous air embolism in radiological investigations of previously published case reports on cerebral air embolism between 1991 and 2001. The cases had to meet the conditions of a history of CVC, consecutive neurological symptoms, CT-diagnosed cerebral air embolism, no diagnosed patent foramen ovale, and exclusion of neurosurgical procedures. The experimental investigation supported the hypothesis that air bubbles entering the venous circulation via a CVC have the potential to rise retrograde depending on air bubble size and local blood flow velocity. The hypothesis is also supported by another case report and by the findings of two studies that describe ascending asymptomatic venous air embolism after injection of intravenous fluids. After acknowledging several limitations in this investigation, the authors still advise that whenever CVC-related venous air embolism is followed by neurological sequelae, retrograde cerebral air embolism should be considered a differential diagnosis to paradoxical arterial air embolism in the brain. 1 figure, 1 table, and 18 references