Boid and crotaline snakes possess two distinct types of organ evolved to image radiant electromagnetic energy: the lateral eye, which responds to visible light, and the pit organ, which responds to infrared radiation. While infrared imaging may allow accurate predatory targeting in complete absence of visual information, both infrared and visual information are probably normally involved in prey targeting. We examined the roles of vision and infrared imaging in Python molurus predatory performance under conditions of (1) high visual contrast; (2) very low visual contrast; (3) complete blinding; (4) experimental monocular occlusion; and (5) congenital monocularity. Normally sighted pythons were equally successful at targeting white (BALB/c) and black (C57BL6/J) mice (Mus domesticus) against a black background. Binocularly occluded snakes exhibited strike angles and distances similar to non-occluded snakes, but exhibited lower strike success, suggesting that high visible contrast is not required for accurate targeting, but that precise targeting depends to some degree upon visual information. Strike angles, distances and latencies were indistinguishable between snakes subjected to experimental monocular occlusion and normally sighted snakes. However, snakes congenitally lacking one eye preferentially targeted on the sighted side. Thus, accurate targeting of highly mobile homeothermic prey by Python can be accomplished with little or no visual information, but performance can be affected by complete visual deprivation or by alteration of visual input during development. The developmental effects of early visual deprivation in this system provide a novel opportunity to investigate the neural integration of two electromagnetic radiation-imaging systems in a single animal.