A positive sonographic Murphy sign, the presence of maximal tenderness elicited over a sonographically localized gallbladder, has been reported to be a helpful adjunctive finding in patients with proven acute cholecystitis who are evaluated with ultrasonography. We evaluated 200 patients with right upper quadrant pain, thought to be acute cholecystitis. Results of ultrasound examinations and subsequent follow-up were tabulated. The sensitivity of the sonographic Murphy sign in acute cholecystitis was 86% with a specificity of 35%, positive predictive value of 43%, and negative predictive value of 82%. The sensitivity of the sonographic findings, including stones, gallbladder wall edema, and pericholecystic fluid collections, was 93%, a specificity of 53%. The combination of the Murphy sign accompanied by gallstones yielded a specificity of 77%. The large number of false positives, and only moderate improvement in specificity when accompanied by gallstones, makes this sign unreliable in separating acute from chronic cholecystitis.