Reptiles offer a rich diversity for the study of chemoreception, and snakes are a particularly appropriate group for comparative, evolutionary, genetic, developmental, and mechanistic studies. A long-term program of research is described that attempts to integrate these approaches, focusing on the widespread North American genus Thamnophis (Natricinae). Prior to their first meal, neonatal snakes respond to aqueous surface substances from species-typical prey with increased tongue-flicking and open-mouth attacks; these responses are mediated by the vomeronasal organ. Such responses predict what prey snakes will eat and can also predict relative prey preference. Species, population, litter, and individual differences exists and are important at different levels of analysis. Chemoreceptive responses are heritable, although they may show different developmental trends. Some species respond to prey types they do not eat in nature. In the earthworm specialist, T. butleri, response to fish chemicals can be interpreted as a chemoreceptive response inertially inherited from ancestral species, decoupled from prey capture techniques, and in the process of being lost. Ontogeny and experience can modify behavior of the neonate in various ways. Feeding experience can alter response to some prey more than others, and ambient prey odor may shift prey preference. Psychophysical studies show that prey preference and threshold sensitivity to prey chemicals can be independent and differ between closely related species, indicating that neural tissue is devoted to recognition of specific types of prey. In site choice tests, garter snakes can also discriminate between feces derived from conspecific snakes fed similar or different diets.(ABSTRACT TRUNCATED AT 250 WORDS)