The West Indian and South American lizards now referred to the iguanid genus Leiocephalus are separated from one another in many features of the skeleton and integument. These differences include the shape of the tooth crowns, the presence of an anterolateral process on the coronoid bone, the position of the temporal muscle insertion on the lower jaw, the positional relationship of the premaxillary and nasal bones, the shape of the roofing part of the parietal bone in adults, the configuration of the xiphisternum, the length and number of the parasternal ribs, the presence of a crest or spine above the neural arch of the autotomic caudal vertebrae, the contact of nasal and rostral scales, and the number and distribution of scale organs. Other differences, while not entirely diagnostic, show diverging trends in the two groups: the presence of pterygoid teeth, the surface of the dorsal head scales, keeling of the ventral scales, the presence of nuchal and antebrachial folds, the size of the postfemoral scales, and the enlargement of the subdigital lamellae. Comparison of the insular and continental species referred to Leiocephalus with other tropidurine genera, Stenocercus, Tropidurus, Liolaemus, Phrynosaura, Ctenoblepharis, Proctotretus, Platynotus, Plica, Uranoscodon, and Urocentron, indicates that each group more closely resembles some other genus than it does the other group. The West Indian species are the most distinctive group of all tropidurines; they appear to be most closely allied to Liolaemus. The South American species very closely resemble Stenocercus. These facts call for the generic separation of the West Indian and South American species now referred to Leiocephalus. The earliest available generic name for the insular forms is Leiocephalus Gray, 1827 (type-species L. carinatus). The monotypic genus Hispaniolus is placed in the synonymy of Leiocephalus. The earliest available generic name for the continental species is Ophryoessoides Dumeril, 1851 (type-species 0. tricristatus). Possibly, some of the species now referred to Stenocercus should be referred to Ophryoessoides.