The causal prophylactic activity of the novel hydroxynaphthoquinone, 566C80, was assessed against the exo-erythrocytic (EE) stages of Plasmodium berghei cultured in the human hepatoma cell line, HepG2. 566C80 was found to be highly active as an inhibitor of EE development and was more active than the established causal prophylactic pyrimethamine. A 566C80 concentration of 1.85 x 10(-9) M, added 3 h after sporozoite invasion, reduced the numbers of EE forms visible at 48 h by 50 degrees o, while the equivalent concentration of pyrimethamine was 1.95 x 10(-8) M.