Multiple sclerosis (MS) is an immune-mediated disease of the white matter in the brain that can have a progressive course. However, the progression of relapsing-remitting (RR) MS into relapsing-progressive (RP) MS might represent a more fundamental change in disease activity, i.e. decay of vulnerable neurons and oligodendrocytes. In RP-MS, this may imply that the major loss of brain tissue structure is caused by a combination of demyelination and cellular loss, both of which are likely to cause disability in MS. We used the PET isotope cobalt-55 (Co) as a calcium (Ca) tracer to visualize brain tissue damage, based on the fact that Ca influx is essential in both cell death and T-lymphocyte activation in MS. The aim of this study was to determine whether Co-PET detects any RP-MS lesions and, if so, to assess any correlation with the progression rate (PR) of the disease and with MS lesions as detected by MRI. Seven RP-MS patients (Poser) with EDSS > 4.0 (Kurtzke) and 7 healthy controls underwent MRI (Miller, Barkhof) and Co-PET. Comparison of both image modalities was made by merging. Co-PET lesion frequency was assessed and correlated with the PR of the disease. Co-PET demonstrated significantly more lesions in the MS brain than in the healthy brain, both periventricular and cortical. Every single MRI lesion could be retrieved as a Co-PET lesion. The Co-PET lesion frequency correlated significantly with PR. Our pilot study possibly suggests Co-PET as a tool in estimating disease activity in RP-MS.(ABSTRACT TRUNCATED AT 250 WORDS)