This story is about the twentieth-century ethnobotanist, Richard Evans Schultes (1915–2001), and his research on hallucinogenic plants. Ethnobotany can contribute directly to science and technology studies in that the discipline makes cultural ways of knowing its scientific subject. Ethnobotanists must learn about plants through people, and are not able to conceal their interactions with indigenous informants and other ethnobotanists. I focus on an ‘enigma’ that Schultes presented, concerning the peculiar ability of indigenous Amazonians to distinguish between local varieties of vine that he was unable to tell apart, notably those used to prepare the hallucinogenic beverage ayahuasca. The enigma describes a complicated and irresolvable question thrown up at the uneasy intersection between different ways of knowing about the world, and shows how modern scientific travellers might navigate – or fail to navigate – the uncertain passage between them. Together with Schultes’s accounts of his own non-ordinary states of consciousness elicited by ayahuasca, and his writings on the Victorian botanist Richard Spruce, I chart an epistemological gulf between Schultes’s modern scientific cosmology and that of his Amazonian informants. In describing his inability to learn about the ayahuasca varieties from Amazonians, Schultes’s enigma traces the very limits of the ethnobotanical discipline and reveals the fragility of the processes by which scientific naturalists might impose categories such as ‘nature’ and ‘culture’.