BACKGROUND: There are currently limited human in vivo data characterizing the role of the meniscus in load distribution within the tibiofemoral joint. Purpose/Hypothesis: The purpose was to compare the strains experienced in regions of articular cartilage covered by the meniscus to regions of cartilage not covered by the meniscus. It was hypothesized that in response to walking, tibial cartilage covered by the meniscus would experience lower strains than uncovered tibial cartilage. STUDY DESIGN: Descriptive laboratory study. METHODS: Magnetic resonance imaging (MRI) of the knees of 8 healthy volunteers was performed before and after walking on a treadmill. Using MRI-generated 3-dimensional models of the tibia, cartilage, and menisci, cartilage thickness was measured in 4 different regions based on meniscal coverage and compartment: covered medial, uncovered medial, covered lateral, and uncovered lateral. Strain was defined as the normalized change in cartilage thickness before and after activity. RESULTS: Within each compartment, covered cartilage before activity was significantly thinner than uncovered cartilage before activity ( P < .001). After 20 minutes of walking, all 4 regions experienced significant cartilage thickness decreases ( P < .01). The covered medial region experienced significantly less strain than the uncovered medial region ( P = .04). No difference in strain was detected between the covered and uncovered regions in the lateral compartment ( P = .40). CONCLUSION: In response to walking, cartilage that is covered by the meniscus experiences lower strains than uncovered cartilage in the medial compartment. These findings provide important baseline information on the relationship between in vivo tibial compressive strain responses and meniscal coverage, which is critical to understanding normal meniscal function.