Observations of two of the endemic species of lizards of Malpelo Island provide new information on their natural history, ecology, and population size. Anolis agassizi, the most abundant and broadly distributed lizard, feeds mainly on insects and excrements of marine birds. It sleeps on large rocks, surfaces on hills or on man-made structures and, although it does not defend perch sites like most Anolis do, it does show preferences for high perches where, among other activities, it carries out copulation. Diploglossus millepunctatus, the largest and least abundant lizard, is an opportunistic-predator and scavenger that has a remarkable relationship with the land crab of the island (Johngarthia malpilensis) which it not only eats, but also competes with it for food. Behavior, higher density, larger body size and weight of individual D. millepunctatus living close to cabins suggest that these lizards accommodate to the presence of people by feeding on left-over food.