We have compared technetium-99m (99mTc) red blood cell (RBC) venography to serial impedance plethysmography (IPG) in 110 consecutive patients with a first episode of clinically suspected deep vein thrombosis (DVT). IPG was performed at Day 0 and, if abnormal, contrast venography was also performed to rule out a falsely positive result. Patients with an initially normal IPG had the test repeated at Days 1, 3, 5 to 7, and 10 to 14. Contrast venography was not performed and anticoagulant treatment was withheld in all patients who remained normal during repeated IPG testing. Technetium-99m RBC venography was performed at Day 0 in patients with an initially abnormal IPG and during the period of serial IPG testing in those with an initially normal IPG. The sensitivity of [99mTc]RBC venography for proximal DVT was 0.68, with 95% confidence limits (CL) from 0.48 to 0.89. Specificity was 0.88 (95% CL from 0.81 to 0.95). When the findings of [99mTc]RBC venography for the entire lower extremity were compared to the reference method, the sensitivity increased to 0.90 (95% CL from 0.82 to 0.97) but the specificity decreased to 0.56 (95% CL from 0.51 to 0.62). Technetium-99m RBC venography is a sensitive but less specific method for detecting DVT of the entire lower extremity. An abnormal [99mTc]RBC venogram, particularly in the calf region, should always be confirmed by another diagnostic method.