Magnetic resonance imaging (MRI) was used to evaluate the efficacy of systemic lymphoblastoid interferon therapy in chronic progressive multiple sclerosis. The clinical outcome of this trial has been reported previously. Thirty-six patients with chronic progressive multiple sclerosis were treated with interferon daily for 6 months and 27 received placebo. Patients had MRI at the outset of the study and after 6 and 24 months. Lesion activity and changes in lesion load were determined. As the study progressed, both the interferon- and the placebo-treated group developed more active lesions. There was no difference in lesion activity between the two groups. Comparison of lesion load, however, showed a trend toward improvement after 6 months for the interferon-treated group. This difference between the two groups had disappeared by the end of the study. We conclude that lymphoblastoid interferon was not effective in decreasing active MRI-detected lesions or in decreasing MRI lesion load in patients with chronic progressive multiple sclerosis.