In guinea pigs immunized with myelin basic protein (MBP) in complete Freund's adjuvant, experimental allergic encephalomyelitis (EAE) shows a characteristic clinical and pathological course. This study characterized the proton nuclear magnetic resonance (NMR) properties of the central nervous system prior to the onset of clinical signs of EAE. At this time (Days 7-9), the blood brain barrier is disrupted. The effects of the injection of paramagnetic contrast agents gadolinium-DTPA and gadolinium-deferoxamine on the tissue NMR relaxation times were examined. Both proton T1 and T2 relaxation times were prolonged in the spinal cord and the brain prior to the onset of clinical and pathological changes. The largest change was in the thoracolumbar spinal cord where T2 prolongation was 22.9%. Gadolinium-DTPA produced a moderate (5-11%) or marked (9-19%) decrease in control and MBP-treated animals, respectively. Gadolinium-deferoxamine also decreased proton relaxation times but was toxic to all animals, producing respiratory arrest. Changes in proton T2 relaxation times in cord and cerebellum were sufficiently large (greater than 10%) to suggest that they might be visualized by magnetic resonance imaging techniques. We have previously described the changes in proton relaxation times during the acute phase of EAE (S.J. Karlik, G. Strejan, J.J. Gilbert, and J.H. Noseworthy, Neurology 36, 1112 (1986]. This study indicates that proton relaxation times are significantly altered at a time when blood brain barrier disruption occurs prior to the onset of clinical or pathological signs.