Quantitative signal intensity measurements are being utilized in both clinical and research magnetic resonance imaging protocols. This paper addresses three questions in quantitative MRI measurements as evaluated within the knee: 1) the accuracy of quantitative measurements; 2) improvement of accuracy by phantom normalization; and 3) the amount of signal change that is clinically significant. Seven normal subjects were imaged on three different days within a 1-wk period. Test-tube phantoms of manganous chloride (MnCl2) were imaged posterior to the knee and were used to normalize each image. The variation in signal intensity within the same subject averaged 20% for both the anterior cruciate ligament (ACL) and the posterior cruciate ligament (PCL). The phantom variation was approximately 18%. Signal intensity normalization by background subtraction, background division, phantom division, or a combination of subtraction and division did not significantly improve either the phantom variation or the ligament variation. Given that an individual ligament intensity will be measured with standard errors of +/- 20% of its value, we calculated the minimum increase in signal intensity to be considered abnormal relative to a normal ligament. A relative signal increase of 46% can be considered pathologic with 95% confidence. These findings emphasize that quantitative measurements must be carefully assessed when being applied in clinical settings.