Sulfadoxine-pyrimethamine (SP) and co-trimoxazole were both effective in reducing fever, clearing parasitaemia and improving anaemia in children aged < 5 years with uncomplicated malaria in 2 Kenyan endemic sites, Oyugis in the west and Tiwi on the coast. We compared the efficacy of these 2 regimens (in May-July 1998) by evaluating clinical and parasitological responses over 14 days. The combined incidence of parasitological failure for the combined sites for co-trimoxazole was 14/123 (11%) and for SP 23/145 (16%) (RR 0.72, 95% confidence interval [CI] 0.31-1.46, P = 0.289). The 14-day clinical failure rate for the combined sites for co-trimoxazole was 4/123 (3.3%), and for SP 8/145 (5.5%), (RR 1.69, 95% CI 0.91-3.15, P = 0.129). The results indicate that the risk of treatment failure for the 2 regimens was similar. The antimalarial use of co-trimoxazole in uncomplicated malaria needs further investigation, since the 10-12-h elimination half-life of both components should reduce selective pressure for resistance. In addition, use of a 2-day high-dose course, tested previously, requires further study to demonstrate its efficacy.