Indigenous people of southeastern North America drank cassina, a stimulant and emetic decoction that the colonial British termed “black drink.” Though most authors cite Ilex vomitoria Ait. as the botanical source of cassina, confusion persists because some researchers identify the source as I. cassine L. To clarify the link between plant and product, the methylxanthine alkaloid contents of I. vomitoria and I. cassine were compared. Since methylxanthines (i.e., caffeine, theobromine, and theophylline) have pharmacological properties congruent with the recorded effects of cassina consumption, the alkaloids provide a chemical basis for the evaluation of both taxa as sources of the beverage. Methylxanthine levels are higher in I. vomitoria than in I. cassine, and the principal alkaloid of the former is caffeine. Based on its alkaloid content, I. vomitoria is the best-supported candidate source of cassina.