FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.