The difference between the median nerve latency to the second lumbrical muscle and the ulnar nerve latency to the second interosseous muscle (L-I DIFF) was tested in a prospective study to discriminate whether prolonged distal motor latency of the median nerve in patients with polyneuropathy (PNP) reflects an additional carpal tunnel syndrome (CTS). We investigated 92 patients (107 hands) with CTS, 30 patients (34 hands) with PNP, 22 patients (27 hands) with CTS and coexisting PNP (PNP + CTS), and 77 controls (87 hands). L-I DIFF was significantly prolonged in both the CTS and PNP + CTS patients as compared to PNP patients and controls. It proved to be the most specific test to differentiate between diffuse (PNP) and focal (entrapment) nerve disorder.