Functional MRI of the spinal cord is challenging due to the small cross section of the cord and high level of physiological noise. Though blood oxygenation level-dependent (BOLD) contrast has been used to study specific responses of the spinal cord to various stimuli, it has not been demonstrated using a controlled stimulus. In this paper, we use hypercapnic manipulation to study the sensitivity and specificity of functional MRI in the human cervical spinal cord. Simultaneous MR imaging in the brain and spinal cord was performed for direct comparison with the brain, in which responses to hypercapnia have been more extensively characterized. Original contributions include: (i) prospectively controlled hypercapnic changes in end-tidal PCO2, (ii) simultaneous recording of BOLD responses in the brain and spinal cord, and (iii) generation of statistical maps of BOLD responses throughout the brain and spinal cord, taking into account physiological noise sources. Results showed significant responses in all subjects both in the brain and the spinal cord. In anatomically-defined regions of interest, mean percent changes were 0.6% in the spinal cord and 1% in the brain. Analysis of residual variance demonstrated significantly larger contribution of physiological noise in the spinal cord (P < 0.005). To obtain more reliable results from fMRI in the spinal cord, it will be necessary to improve sensitivity through the use of highly parallelized coil arrays and better modeling of physiological noise. Finely, we believe that the use of controlled global stimuli, such as hypercapnia, will help assess the effectiveness of new acquisition techniques.