The cells in the midsubstance portion of skeletal ligaments typically have elongated shapes, but where ligaments insert into bone the cells appear very rounded and the tissue phenotype is that of fibrocartilage. Between the midsubstance and the insertions there is a gradient in cell shape and tissue phenotype that has been hypothesized to reflect a gradient of mechanical stresses. To test this hypothesis, cell shapes (an index of tissue phenotype) were quantified in the central part of the femoral insertion of the rabbit medial collateral ligament by computer-assisted histomorphometry. Morphometric measurements were correlated with the mechanical stresses and strains in the central part of the insertion as predicted by finite element analysis. Throughout the ligament the direction of the predicted principal tensile stresses coincides with the direction of the collagen fibers which curve from the midsubstance to meet the femur at nearly right angles. Principal compressive stresses also occur within the ligament: the highest are localized near the bone; the lowest in the midsubstance. The areas with the roundest cells correspond to the areas with the highest principal compressive stresses in the model; the areas with the flattest cells correspond to the areas with the lowest compressive stresses in the model. A correlation between cell shape and mechanical stresses suggests that physiological loading of the MCL is important for the maintenance of tissue phenotype throughout this insertion. We theorize that the cells in ligament insertions adapt to the prevailing local mechanical environment.