In an open, randomized, clinical trial, conducted in New Halfa, eastern Sudan, in September-October 2004, the efficacies and adverse effects of artesunate plus sulfadoxine-pyrimethamine (SP), in the treatment of uncomplicated, Plasmodium falciparum malaria, were compared with those of SP alone. Patients were randomized to receive either artesunate (4 mg/kg. day) on days 0-2 plus SP (25 mg sulfadoxine/kg) on day 0 or the SP alone, and then followed-up for 28 days. Sixty patients completed follow-up. Compared with the 30 given artesunate plus SP (ASP), the 30 given SP alone were much more likely to be febrile (30% v. 3.3%; P=0.006) and parasitaemic (50% v. 6.7%; P<00001) on day 1. By day 3, 16.7% of the patients given SP alone were still febrile and 6.7% of them were still parasitaemic, although all the patients given ASP were then afebrile (P=0.02) and aparasitaemic (P=0.1). Five (16.7%) of the patients treated with SP alone but none of those given ASP appeared to be treatment failures (P<0.05). Parasite genotyping revealed that four of the five apparent treatment failures were true recrudescences but the other represented a re-infection detected on day 28. The true frequencies of cure by day 28 were therefore 100% for ASP and 86.7% for SP alone (P=0.02). Adverse effects of treatment (nausea, itching and giddiness) were observed with similar frequencies in the two treatment arms (10.0% of the patients given ASP v. 13.3% of the patients given SP alone; P>0.05). The frequencies of gametocytaemia during follow-up were, however, much lower in the ASP arm than in the SP-only (0.0% v. 23.3%; P=0.005).Thus, although the problems posed by adverse effects were similar in the two treatment arms, ASP appeared markedly better, in terms of fever- and parasite-clearance times and the prevalence of post-treatment gametocytaemia, than SP alone.