The anterior cruciate ligament is a complex tissue composed of structural proteins, proteoglycans, and cells. The histology of the human anterior cruciate ligament is characterized by the specific distribution and density of the fibroblast phenotype as well as by the unique organization of the structural proteins. A notable finding of this study was the identification of three histologically different zones along the anteromedial bundle as it coursed from the femoral to the tibial attachment. Two of the zones, the fusiform and ovoid, were located in the proximal one-quarter of the bundle; the third zone, the spheroid, occupied the distal three quarters of the bundle fascicles. The fusiform cell zone was characterized by a high number density of longitudinally oriented cells with a fusiform-shaped nucleus, longitudinal blood vessels, and high crimp length. The cytoplasm of the cells in this zone appeared to be intimately attached to the extracellular collagen and followed the crimp waveform of the fibers. Fusiform cells were noted to stain positively for the alpha-smooth muscle actin isoform in this region, particularly at areas of crimp disruption. The ovoid cell zone was characterized by a high number density of cells with an ovoid-shaped nucleus, longitudinal vessels, and a high crimp length. In this zone as well, the cytoplasm of the cells appeared to follow the waveform of the adjacent collagen. Ovoid cells were noted to stain positively for the alpha-smooth muscle actin isoform in this region. The spheroid cell zone was characterized by a low density of spheroid cells, few blood vessels, and short crimp length. Cells were noted within and among fascicles, as well as within lacunae. In selected areas, as many as 50% of the cells in this region stained positively for the alpha-smooth muscle actin isoform. This is also the first report of cells expressing the alpha-smooth muscle actin isoform in the intact human anterior cruciate ligament. This specific type of contractile actin, initially identified only in smooth-muscle cells, pericytes, and myofibroblasts, was seen in cells with various morphologies and predominantly in cells located at areas of crimp disruption. Further work is necessary to elucidate the role of the various fibroblast phenotypes in the maintenance of the human anterior cruciate ligament.