The response of P. Falciparum to chloroquine (CQ) and pyrimethamine-sulphadoxine (FSD) in vivo was investigated in 173 indigenous uncomplicated malaria patients at Sololo Hospital, Moyale district in northern Kenya, All the patients were symptomatic and parasitaemic. They were divided in two age groups (children <10 years, adults >10 years). They were randomly assigned to receive either CQ or PSD standard treatment and then followed up at 7 and 14 days. In the child group, out of 91 patients enrolled, 65 (71.4%) completed the seven-day study; among these 38 (17 females and 21 males with mean age of 41.9 months) were treated with CQ and 27 (11 females and 16 males with mean age 39.1 months) with PSD. Parasites were significantly (p<0.001) more resistant to CQ (18/38, 47.4%) than PSD (0/27, O%). In the adult group, out of 82 patients enrolled, 54 (65.9%) completed the a-day-study, and among these 27 (10 females and 17 males with mean age of 22.5 years) were treated with CQ and 27 (ii females and 16 males with mean age of 23.2 years) with PSD. Parasites were significantly (p=0.01) more resistant to CQ (7/20, 25.9%) than PSD (0/27, 0%). Overall, considering the 119 patients who completed the follow-up, the resistance of P. falciparum was significantly higher (p<0.001) to CQ (25/65, 38.5%) than to PSD (0/54, 0%). Out of the 94 patients with negative slide at day 7, fifty seven came at the control of the day 14 (30 children and 27 adults). Among them, 22 were in CQ group and Eve were found positive (22.7%), while the 35 patients in FSD group all tested negative (p=0.006). The resistance to CQ in the children group was 25% (p=0.05) and 20% in the adult group (p=0.13). We conclude that the significant parasitological resistance to CQ in the area under study questions the continued use of CQ as first line antimalarial treatment. On the contrary, PSD can still he considered a very effective drug against P. falciparum in northern Kenya.