Ninety-two children with complicated, but not cerebral, Plasmodium falciparum malaria, aged 1-9 years, were recruited between August 1992 and December 1994 to an open, randomized trial of parenteral chloroquine (28), pyrimethamine-sulfadoxine (P-S) (36) and quinine (28). The median fever clearance time was shorter for chloroquine (27 hours) than for quinine (42 hours) or for P-S (36 hours) (P = 0.02 and P = 0.06, respectively). The parasite clearance times were similar for chloroquine and P-S, but significantly shorter for chloroquine compared with quinine (54 hours vs 66 hours) (P = 0.007) and for P-S compared with quinine (42 hours vs 66 hours) (P < 0.001). However, three children who received chloroquine and three who received P-S required a change to treatment with quinine because of a clinical failure of their initial treatment. Four children died, one in the chloroquine group, one in the quinine group and two in the P-S group. Despite a high level of chloroquine resistance in the community, the majority of Gambian children with complicated malaria responded satisfactorily to parenteral chloroquine given under supervision. The clinical failure rates of chloroquine and P-S were similar. Parenteral chloroquine and P-S remain adequate treatments for complicated, non-cerebral malaria in Gambian children, provided children can be kept under close clinical observation so as to detect early any treatment failures. Parenteral P-S has the advantage that only one dose is required.