Clociguanil (BRL 50216, WR 38839) is an antimalarial compound, a derivative of N-benzyloxydihydrotriazine, developed by Beecham Pharmaceuticals. Mode of action studies indicated that clociguanil is a dihydrofolate reductase inhibitor of Plasmodium and is capable of marked potentiation with a selected sulphonamide against both the sensitive N strain and the cycloguanil-resistant B line of P. berghei. A combination of clociguanil and sulphadiazine prevented the development of parasitemia caused by P. falciparum in humans. The subsequent development of clociguanil was discontinued because of a relatively short half-life in man and lack of suppression of pre-erythrocytic schizogony of a strain of P. falciparum resistant to chloroquine, pyrimethamine, and proguanil.