A single score is desirable for evaluating progression in clinical trials of MS therapy. Our objective was to develop a more sensitive scoring that would reflect clinical assessment of relative severity of disability. An Illness Severity Score (ISS) was developed as a sum of weights corresponding to ratings of Kurtzke Disability Status Scale and Functional Systems Scales and phase of illness. Weights were computed from clinical comparison of pairs of patients. The score was standardized to have mean 50 and standard deviation 10 in a single clinic population. Score reproducibility (correlation = 0.93) was evaluated by two independent scorings of several patients. The ISS was satisfactory as the primary assessment in a small-scale clinical trial.