The need for reliable markers of disease activity in multiple sclerosis (MS) to better guide basic research, diagnosis, treatment, and monitoring of therapy is well-recognized. A recent European Charcot Foundation Symposium (Body fluid markers for course and activity of disease in multiple sclerosis (Madrid, Spain, October 2-4, 1997) organized by the European Charcot Foundation and the Fundación Española de Esclerosis Múltiple (the Spanish Multiple Sclerosis Foundation) brought together experts in the field to review the state of the art for the technology measuring markers in body fluids. An array of different approaches was presented to measure a wide diversity of classic and novel marker molecules, including cytokines, adhesion molecules, myelin compounds, and free antibody light chains, in either blood, urine, or cerebrospinal fluid. Here, recent progress in these approaches is assessed in the context of distinct pathophysiological stages of the disease, the requirements which such molecules and assays should ideally meet, and the practical and conceptual challenges which they face. Recommendations for further improvements are described.