Amodiaquine, a 4-aminoquinoline which has been shown to be effective in treating infections with chloroquine-resistant strains of Plasmodium falciparum, was evaluated against chloroquine-resistant infections in children in Zanzibar, Tanzania, during July 1982. A 25-mg base/kg dosage of amodiaquine produced parasite clearance in 34 of 38 (89%) children in a mean of 2.8 days. When followed for 28 days, 15 of 38 (39%) children were completely cured of their infection as judged by the absence of renewed parasitemia. The parasite clearance rates produced by amodiaquine were significantly higher than those observed in a comparison group of children treated with 25 mg base/kg chloroquine. There was, however, no difference in the cure rates in the chloroquine and amodiaquine groups. Despite the enhanced parasite clearance rate, amodiaquine is not sufficiently more effective against Zanzibari strains of P. falciparum to replace chloroquine. Other alternative drugs must be evaluated to define the optimal malaria therapy regimen on Zanzibar.