The purpose of this study was to determine the validity of tests or a combination of tests far the diagnosis of carpal tunnel syndrome. Three groups of 50 subjects each were studied: group 1 had definite carpel tunnel syndrome as defined by history, clinical presentation, and improvement of symptoms following carpal tunnel release; group 2 had a variety of nontraumatic upper extremity disorders other than carpal tunnel syndrome; and group 3 subjects were asymptomatic healthy volunteers, Subjects submitted a self-administered hand diagram, and were queried about night pain, symptom duration, and coexistent medical conditions. Phalen's test, Tinel's sign, Durkan's compression test, and Semmes-Weinstein monofilament testing both before and after a Phalen's maneuver for 5 minutes were performed an each subject. Grip and pinch strengths were measured. Univariate analysis of groups 1 and 2 showed that the tests with the highest sensitivity were Durkan's compression test (89%), Semmes-Weinstein testing after Phalen's maneuver (83%), and hand diagram scares (76%). Night pain was a sensitive symptom predictor (96%). The most specific tests were the hand diagram (76%) and Tinel's sign (71%). Analysis of groups 1 and without group 2 increased the specificity and predictive value of a positive test. A regression model was used to develop a multivariate equation with 4 variables. If a patient has an abnormal hand diagram, abnormal sensibility by Semmes-Weinstein testing in wrist-neutral position, a positive Durkan's test, and night pain, the probability that carpal tunnel syndrome will be correctly diagnosed is 0.86. If all 4 of these conditions are normal, the probability that the patient has carpal tunnel syndrome is 0.0068. We found that the addition of electrodiagnostic tests did not increase the diagnostic power of the combination of 4 clinical tests. (J Hand Surg 1999;24A:704-714. Copyright (C) 1999 by the American Society for Surgery of the Hand.).