Several reports have confirmed the existence of chloroquine resistant Plasmodium falciparum malaria in Bombay. In the management of these cases, of the therapeutic options available, sulfadoxine-pyrimethamine (SP) (administered as a single dose) is preferred, since quinine has to be administered over a period of 7 days while mefloquine is yet to be marketed in India. With increasing reports of falciparum malaria resistant to SP from Thailand and Africa, the present study was conducted to determine the efficacy of SP in the treatment of chloroquine resistant falciparum malaria cases in Bombay. 17 uncomplicated falciparum malaria patients documented to be resistant to chloroquine (10 RI, 5 RII and 2 RIII) by the WHO (1973) in-vivo extended field test criteria and by estimation of plasma chloroquine levels by High Performance Liquid Chromatography were included in the study. These adult patients were then treated with a supervised single dose of 3 tablets of SP and peripheral blood smears were then repeated on days 3, 4, 5, 7, 14, 21, 28, 35 and 42 after treatment. 14 patients responded and were sensitive while 3 patients showed RII grade resistance to SP. These 3 patients then responded to a 7 day course of quinine (30 mg/kg/day)+doxycycline (100 mg/day). These results thus document that SP can be used as an effective second-line antimalarial drug. However one should monitor the patient for plasmodial resistance to sulfadoxine-pyrimethamine.