Magnetic resonance imaging (MRI) of the cerebrum, cerebellum, brain stem, and upper cervical cord was performed in 62 individuals with clinically definite chronic, progressive multiple sclerosis (MS). The total area of MRI-demonstrated lesions was measured from film enlargements for each region using an interactive image analysis system. While the MRI was abnormal in 60 (97%) of 62 patients, the visual-evoked potentials in 51 (85%) of 60 patients, the brain stem auditory-evoked potentials (BAEPs) in 24 (46%) of 52 patients, and the somatosensory-evoked potentials (SSEPs) in 45 (89%) of 54 patients, an abnormal intra-blood-brain barrier (BBB) IgG synthesis rate, IgG oligoclonal bands, or both were found in all 62 patients. The total area of MRI abnormality in the cerebrum was significantly correlated only with the intra-BBB IgG synthesis rate, abnormal visual-evoked potentials, impaired performance on the Symbol Digit Modalities Test (SDMT), and one test of standing duration in the quantitative examination of neurologic function (QENF). The brain stem lesion area correlated with the Kurtzke expanded disability status scale and brain stem functional systems score, the ambulation index, abnormal BAEPs, and impaired performance on the SDMT as well as multiple tests of upper and lower extremity function in the QENF. The cerebellar lesion area correlated with impaired performance on the SDMT and primarily upper extremity testing in the QENF.(ABSTRACT TRUNCATED AT 250 WORDS)