17 Wild-harvested plants are a globally valuable source of food and medicines and provide livelihoods 18 for millions of people. Lophophora williamsii (peyote) is a small psychoactive cactus native to Mexico 19 and Texas, USA, with considerable cultural, religious and medicinal significance to many indigenous 20 peoples of North America. Peyote, like many plant species globally, is facing multiple threats and is 21 in decline due to legal and illegal harvesting pressure as well as habitat conversion to grazing, 22 agriculture and other economic land uses. Most published studies on peyote have focused on the 23 plant's anthropological, chemical and medical aspects. Surprisingly little is known about the ecology 24 of this species, despite it being currently listed as Vulnerable on the IUCN Red List. Our study 25 addresses this gap by providing the first detailed comparison of peyote populations growing in two 26 distinct ecosystems in the USA: South Texas (Tamaulipan thornscrub) and West Texas (Chihuahuan 27 desert). We highlight regional differences, whereby in West Texas plants at the surveyed sites plants 28 were larger and densities were higher than in South Texas and note significant variability both within 29 and between study sites. We also find significant effects of temperature and precipitation on plant 30 size. Meaningful data about population size and structure across the range of habitats is the first 31 necessary step in order to address a major conservation challenge of sustainable management of 32 an overexploited resource. We conclude that urgent conservation and restoration efforts involving 33 Native Americans and local landowners are needed to secure long-term survival of this vulnerable 34 cactus. Keywords 35 Cactaceae, Lophophora williamsii, plant conservation, population ecology, sustainable harvesting, 36 ethnobotany.37 Global demand for wild-harvested resources is increasing, while natural habitat for such resources 38 is being lost to a variety of anthropogenic disturbances [1][2][3]. More than 28,000 plants are used for 39 medicinal purposes worldwide, many more have cultural and/or religious significance [4]. 40 International Union for Conservation of Nature (IUCN) estimates that at least 15,000 of these are at 41 risk of extinction from a combination of over-harvesting, habitat destruction and climate change 42 [5]. Sustainable harvesting of wild species is a major global conservation challenge, yet the first 43 necessary step for this is understanding distribution and population structure of species in question. 44 Poor knowledge of ecology and population dynamics of plant species greatly limits conservation 45 actions and can result in inappropriate decisions and policies that do not ensure long-term survival, 46 as well as a waste of limited resources allocated to conservation [6]. Baseline population data across 47 the whole distribution range of species are crucial for developing and testing conservation 48 interventions, long-term monitoring and species responses to climate chang...