Human-plant interactions have figured prominently in our species' evolution and they continue to influence the contemporary geographical patterns of human biodiversity. The domestication of particular plant taxa has genetically modified those taxa and intensified human contact with specific plants and their endogenous bioactive allelochemicals (secondary plant compounds). This contact, sustained over multiple generations of humans and plants has provided, on occasion, unique opportunities for amplified interactions of microevolutionary importance. In this paper, a theoretical overview of these interactions is presented and four case studies are detailed as examples of local potentially coevolutionary specificity. The first set of case studies include two human-plant diads: 1) salivary proline-rich proteins and carcinoma in East Asian ethnic groups and ingestion of tea (Camellia sinensis) flavonoids (polyphenols) and 2) HLADQZ+ phenotypes and celiac disease in Northern Atlantic European ethnic groups and ingestion of wheat (Diticum aestiuum) A-gliadin peptides. Since established human-plant interactions frequently involve a third species, the second set of case studies includes two human-plant-parasite triads: 1) red blood cell GGPD variants similar to Gdmea and favism in Mediterranean ethnic groups and ingestion of fava bean (Vicia faba) glycosides and exposure to Plasmodium falciparum malaria and 2) HbPS phenotypes and sickle cell anemia in West African ethnic groups and ingestion of cassava (Manihot esculenta) cyanogenic glucosides and exposure toPlasmodium falciparum malaria.The rationale for the systematic study of the reciprocal interactions between humans and plants is well-grounded in biological anthropology. Human survival and evolutionary change has always been contingent upon successful interactions between hominids and other life forms. These interactions have shaped the biology and behavior of each participating species in ways that we are just beginning to identify, quantify, and understand. However, in spite of the relevance of human-plant interaction studies to understanding the process of human diversification and the geographical patterns of human 0 1996 Wiley-Liss, Inc.variability, research in this area is still at a very early stage of development.' This paper is in two parts: Part one focuses on the theoretical premises for biocultural evolutionary ecology and the potential for human-plant coevolution. Part two dis-'In fact, the only other published article specifically dealing with coevolution in humans is Budiansky's (1994) paper on the coevolution ofhumans and domesticated animals. This paper was presented a t the 1993 American Veterinary Medical Association Animal Welfare Forum. Most coevolutionary studies have discussed insect-plant interactions, plant-pathogen interactions, and more recently, mammalian herbivore-plant interactions.0 1996 WILEY-LISS, INC.