In The Gambia co-trimoxazole is used widely to treat children with an acute respiratory infection (ARI). Because malaria may sometimes be mistaken for ARI, some children with malaria are treated with co-trimoxazole. Therefore, we investigated the sensitivity of Gambian isolates of Plasmodium falciparum to this drug. Six days after the start of treatment with co-trimoxazole 3.3% of blood films of 65 asymptomatic subjects were positive, and 7.7% were positive after 21 d. One of 10 patients with ARI and malaria treated with co-trimoxazole had a positive blood film 3 d after the start of treatment but was negative thereafter. All 10 patients recovered satisfactorily. Thirty 'wild' isolates of P. falciparum were tested in vitro against co-trimoxazole at a ration of 5 parts sulphamethoxazole (SMZ) to 1 part trimethoprim (TMP). The mean EC50s, using a 36 h assay, were 1.2 x 10(-7) and 2.5 x 10(-8) M for SMZ and TMP respectively. When a [3H]hypoxanthine incorporation assay was employed, values of 5.7 x 10(-7) M for SMZ and 1.2 x 10(-7) M for TMP were obtained. These values are well below the peak plasma concentration. Our findings suggest that co-trimoxazole is effective against falciparum malaria in The Gambia. However, if it were to be used widely, the parasite would be likely to develop resistance to this and other dihydrofolate reductase inhibitor antimalarials.