In March 1993, sulphadoxine/pyrimethamine (SP) replaced chloroquine as the first line drug for malaria treatment in Malawi. Since then, the Ministry of Health has been receiving anecdotal and written reports of SP treatment failures in children. To determine whether treatment failure with SP was a widespread problem, children < 5 years of age with axillary temperature > 38.0 degrees C and parasite density > 2000/mm3 attending the outpatient clinics of the Mangochi and Karonga District Hospitals were enrolled in the study with parental consent. These were then followed for 28 days or until they failed clinically. Of 159 patients enrolled, 145 (91.2%) were followed for 28 days or until clinical failure. Of these, none had RII resistance and 3 (1.9%) had RIII resistance: 2/69 (2.9%) in Mangochi and 1/76 (1.3%) in Karonga; 142/145 (97.9%) exhibited RI/sensitive patterns. Of those followed to day 28 or to clinical failure, 77.1% had parasite clearance by day 3 and 98.6% had parasite clearance by day 7. Of those with temperature readings (n = 140), 129 (92.1%) clinically improved on day 3 and 98.6% improved by day 7. Other indicators of clinical improvement (from day 0 to day 3) included, reported increased level of activity in 136 (97.1%) of the children, and mother's impression of child's improvement in 113 (80.7%). Of the 14 patients not followed to day 28 or to clinical failure, 11 were lost to follow-up by day 7. No allergic skin reactions were noted, and no deaths were observed. These data show that after one year of widespread use of SP in Malawi, Plasmodium falciparum parasite resistance remains very low, and therefore contradicts reports of widespread parasite resistance to SP.