Studies of the comparative pharmacology of quinine revealed that rabbits possessed an unusual ability to metabolize this drug. The metabolic derivative formed by rabbit liver in vitro was isolated in pure crystalline form and found to possess a lower toxicity and antimalarial activity than quinine. In collaboration with other laboratories, the structure of this new derivative was established and several analogues synthesized with blocking groups present at the site of oxidation. Certain of these compounds show considerable promise and are still under investigation.