In 1993, Malawi introduced sulphadoxine-pyrimethamine (SP) for the treatment of uncomplicated, Plasmodium falciparum malaria and became the first country in Africa to abandon chloroquine for first-time therapy. This decision produced an urgent need to monitor local P. falciparum for resistance to SP and to establish both clinical and parasitological criteria for drug failure. The parasitological and haematological responses to treatment of malaria in southern Malawi with SP have now been investigated. Children, aged 6-59 months, who attended health-care facilities with uncomplicated infections of P. falciparum alone were enrolled in the study. Each received standard treatment with SP and paracetamol and was followed-up on days 3, 7, 14, 21 and 28 post-treatment. Haemoglobin (Hb) was measured on days 0, 14 and 28. Zinc erythroprotoporphyrin (ZP) was estimated once during follow-up, as an indicator of iron status. Of 107 children enrolled, 84 children (78.5%) were followed for 14 days or until clinical failure. The parasitological success rate amongst the latter was 90.5% (76/84). One child showed poor parasite clearance (with a parasitaemia at day 3 > 25% of that at day 0), one had a low level of persistent parasitemia, and six were parasitaemic on day 14 after being parasite free on day 7. A 14-day follow-up increased the detection of parasitological failure by 7.2%. Haematological recovery on day 14 was not significantly different for parasitological successes or failures. The geometric mean parasite density (GMPD) was significantly lower in children classified as iron deficient (ZP > or = 3.0 micrograms/g Hb) and these children were significantly more likely to be severely anaemic (Hb < 8 g/dl) at day 0. Parasitological responses and haemoglobin levels 28 days after SP treatment were independent of ZP levels. These results show that, 2 years after the introduction of SP in Malawi for the treatment of uncomplicated, P. falciparum malaria, the drug combination remains effective in 90.5% of cases. Iron status did not affect parasitological recovery. Although iron-deficient children were at greater risk of severe anaemia they did not show significantly reduced recovery from malarial anaemia.