The negatively charged contrast agent Gd-DTPA2– distributes inversely to the cartilage fixed charged density. This enables structural cartilage examinations by contrast-enhanced MRI. In line with the development of a clinically applicable protocol for such examinations, this study describes the temporal pattern of Gd-DTPA2– distribution in femoral knee cartilage at three different doses in healthy volunteers. Nineteen volunteers (ages 21–28 years) were examined with a 1.5T MRI system. Quantitative relaxation rate measurements were made in weight-bearing central parts of femoral cartilage using sets of five turbo inversion recovery images with different inversion times. The cartilage was analyzed before and four times (1–4 h) after an intravenous injection of Gd-DTPA2– at single, double, and triple doses: 0.1, 0.2, and 0.3 mmol/kg body weight, respectively. The increase in R1 postcontrast was linearly dose-related at all times. The highest R1 values were registered at 2 and 3 h postcontrast, suggesting 2 h to be optimal in the clinical situation. The triple dose indicated a subtle compartmental difference in men, with higher contrast distribution medially than laterally. Results suggest that the triple dose is needed to detect minor cartilage matrix differences. Magn Reson Med 46:1067–1071, 2001. © 2001 Wiley-Liss, Inc.