OBJECTIVE: To study the effect of weekly injected subcutaneous interferon (IFN)-beta-1a 22 microg on the extent of brain lesions on magnetic resonance imaging (MRI) and the level of serum matrix metalloproteinase (MMP)-9 in patients with secondary progressive multiple sclerosis (SPMS). SUBJECTS AND METHODS: All the 28 Finnish patients participating in the Nordic multicentre trial on the clinical efficacy of weekly IFN-beta-1a (Rebif) 22 microg in SPMS were studied neurologically and by volumetric MRI during a 3-year follow-up. The levels of MMP-9 in serum were measured over the 3-year study. RESULTS: There was no obvious effect on the number of contrast medium-enhancing lesions, the volume of T1 or T2 lesions or level of serum MMP-9, nor was any effect detected on the relapse rate and the Expanded Disability Status Scale (EDSS). Brain atrophy progression was not affected by the treatment. CONCLUSION: The lack of effect on MRI, clinical outcomes or the levels of MMP-9 indicates that subcutaneous administration of low-dose low-frequency IFN-beta-1a is insufficient in controlling either the inflammatory constitutes or the neurodegenerative changes of advanced SPMS.