The SPf66 hybrid malaria vaccine is a polymeric, synthetic protein with amino-acid sequences derived from the pre-erythrocytic and asexual-blood-stage proteins of Plasmodium falciparum. SPf66 has already been found to have a 31% protective efficacy in Tanzanian children aged 1-5 years who lived in an area of intensive malaria transmission. A randomized, double-blind, placebo-controlled trial of SPf66 was carried out in Gambian infants. Overall, 630 children, aged 6-11 months at the time of the first dose, each received three doses of SPf66 or inactivated polio vaccine (IPV). Morbidity was monitored during the following rainy season by means of active and passive case detection. Cross-sectional surveys were carried out at the beginning and at the end of the rainy season. Analysis of efficacy was restricted to 547 of the children (316 receiving SPf66 and 231 IPV). Although the efficacy of SPf66 on the first or only clinical attack was found to be 8% when results were compared with those for the children given the placebo (IPV), the malarial vaccine had no significant effect on fever with any parasitaemia, the overall incidence of clinical attacks, packed-cell volumes, parasite prevalences or spleen rates. Compared with the present vaccine, insecticide-treated bednets appear to offer better prospects for control of malaria in Africa.