The transmission of Plasmodium falciparum was studied in relation to the incidence of severe malaria infections at nine sites in the Kilifi District in Kenya. Intensive mosquito sampling during a one-year period yielded Anopheles gambiae s. l., An. funestus, An. coustani, An. squamosus, An. nili, and An. pharoensis. Anopheles gambiae s.l. was the predominant vector, comprising 98.4% of the total anophelines collected. Overall, 3.5% of 2,868 An. gambiae s.l. collected indoors and 0.8% of 261 collected outdoors contained P. falciparum sporozoites. Transmission was detected during 10 months, with peak periods from June to August and December to January. In eight of the nine sites, entomologic inoculation rates (EIRs) averaged only four infective bites per year (range 0–18); an annual EIR of 60 was measured for the site with the highest intensity of transmission. The incidence of severe malaria infections, ranging from 8.6 to 38.1 per 1,000 children (0–4 years), was not associated with EIRs. At these sites on the coast of Kenya, a high incidence of severe disease occurs under conditions of very low levels of transmission by vector populations. With respect to conventional approaches for vector control in Africa, decreases in transmission, even to levels barely detectable by standard approaches, may not yield corresponding long-term reductions in the incidence of severe disease.