Our aim is to assess the optimal discriminatory sonographic criteria and relevant threshold values in patients with carpal tunnel syndrome (CTS) and to evaluate quantitative ultrasonography (US) as a tool for diagnosis and treatment of patients suffering from carpal tunnel syndrome in comparison with electrophysiological study. Seventy-eight patients with CTS and 78 asymptomatic controls were assessed and underwent ultrasonography of the wrists. All patients and controls completed a self-administered questionnaire. Electrophysiological testing was done for all patients and control subjects. Data from the patient and the control groups were compared to determine the diagnostic relations in patients with CTS and the grade of severity. There was a high degree of correlation between the conduction abnormalities of the median nerve as detected by electrodiagnostic tests, self-administered assessment and the measurement of the cross-sectional area of the nerve by US (P<0.05). Various levels of disease severity could also be illustrated by US, giving confident results for diagnosis, treatment planning and following the patients with CTS. In 16 patients (17%) tenosynovitis/localized swelling in the tendons in the carpal tunnel was the primary cause of CTS. A cut-off point of 10 mm(2) for the mean cross-sectional area of the median nerve was found to be the upper limit for normal values. Based on the results of this study, an algorithm for evaluation and management of CTS has been suggested. High-frequency US examination of the median nerve and measurement of its cross-sectional area should be strongly considered as a new alternative diagnostic modality for the evaluation of CTS. In addition to being of high diagnostic accuracy it is able to define the cause of nerve compression and aids treatment planning; US also provides a reliable method for following the response to therapy.