Several criteria must be met in developing a test battery forr ALS. First, the test items should be designed to answer the specific questions being asked. If questions involve the amount and rate of deterioration, then the test items should generate interval data and show evidence that they reflect change in the disease itself. Second, the reliability of the test items should be carefully determined. Are the variances due to testing errors such as inconsistent positioning or changes in verbal instructions; or do they reflect human performance variation? Third, the test items must be sensitive to small changes, and one must be able to test the very strong as well as the severely debilitated patient. The TQNE was designed to measure degree of disease progression in ALS. The major portion of the protocol consists of isometric force measurement using an electronic strain gauge. Other quantitative segments include tests of pulmonary function, speech rates, and timed activities. Using z-score transformations, we have summarized these test items into five megascores: pulmonary function, bulbar function, timed hand activities, arm strength, and leg strength. Megascores have been used to characterize the natural history of the disease and to judge therapeutic efficacy. Quantitative methods to measure deficit in neuromuscular disease lag far behind other technologic advances in medical research. Future advances in the measurement of neuromuscular deficit depend on the commitment of researchers to invest the time and resources necessary to develop more sensitive and reliable testing techniques.