A useful in vitro method for field evaluation of Plasmodium falciparum sensitivity to pyrimethamine/sulfadoxine is described. Thirty-five Kenyan schoolchildren infected with P. falciparum were treated with this drug combination and followed up for 5 weeks. In vitro tests for sensitivity to these drugs and to chloroquine were performed before starting treatment. All infections cleared within 7 days of treatment, but 5 children had recurrent parasitaemia within 35 days. The original isolates from 4 of these 5 children had an in vitro response to pyrimethamine/sulfadoxine similar to a known strain that was resistant to these drugs; only 4 of the remaining 30 isolates from patients in whom recurrent parasitaemia did not occur had a resistant in vitro response (P = 0.006). In the patient with recurrent parasitaemia whose initial isolate appeared sensitive to pyrimethamine/sulfadoxine, the recurrent isolate had a resistant pattern in vitro, suggesting either reinfection or selection of a resistant subpopulation following treatment. The in vitro response to this drug combination was correlated with the in vitro response to either drug alone and with the in vitro response to chloroquine. Two of the 5 infections with recurrent parasitaemia after initial pyrimethamine/sulfadoxine treatment were resistant to chloroquine in vivo. The in vitro test for pyrimethamine/sulfadoxine should be useful for mapping the spread of multidrug-resistant P. falciparum.