To investigate the pressure threshold for peripheral nerve dysfunction in compression syndromes (carpal tunnel and compartment syndromes), carpal canal pressure was elevated to 40, 50, 60, and 70 mm Hg in normal volunteers. Motor and sensory latencies and amplitudes of the median nerve were evaluated before compression, after 30-240 minutes of compression, and during the postcompression recovery phase. Although some functional loss occurred at 40 mm Hg, motor and sensory responses were completely blocked at a threshold tissue fluid pressure of 50 mm Hg, measured by the wick catheter. In one subject in whom diastolic blood pressure was significantly higher than in other subjects, the threshold pressure was raised slightly. The Semmes-Weinstein monofilament test and the 256-cycle vibratory test were more sensitive than two-point discrimination tests for evaluating peripheral nerve function in this compression model. These results indicate that between 40 mm Hg and 50 mm Hg there exists a critical pressure threshold at which peripheral nerve is acutely jeopardized. Compartment decompression may not be indicated when interstitial pressures are below this level.