Controlled external compression was applied to the median nerve of 16 volunteer subjects. Tissue fluid pressure in the carpal canal was monitored with a wick catheter and pressures of 30, 60 and 90 mm Hg were induced for periods varying from 30 to 90 minutes. Sensory and motor conduction and two-point discrimination were continuously monitored. Tissue compression at 30 mm Hg caused mild neurophysiological changes and symptoms of hand paresthesias. Compression at both 60 and 90 mm Hg induced a rapid, complete sensory conduction block which consistently preceded a motor block by 10 to 30 minutes. Frequently, two point discrimination remained normal until the last stages of preserved sensory fiber conduction. In three cases, a modification of the model utilizing an arm tourniquet, demonstrated that ischemia rather than mechanical deformation was the primary cause of the functional deterioration. It was concluded that there is a critical pressure level between 30 and 60 mm Hg where nerve fiber viability is acutely jeopardized.