The melanization responses of field-captured Anopheles gambiae s.l. toward oocysts of the malaria parasite Plasmodium falciparum or negatively charged (C-25) Sephadex beads were determined. Only two of 431 infected mosquitoes harboured melanized oocysts. However, 90% of field-captured mosquitoes melanized C-25 Sephadex beads. The effects of age, glucose concentration and blood meal on the melanization response of an An gambiae s.s. laboratory colony toward C-25 beads were also assayed. All newly emerged females (which did not blood-feed) melanized the beads. By 4 d postemergence, there was a marked reduction in melanization response, particularly among those mosquitoes that had not blood fed. A blood meal, however, taken by 4-d-old mosquitoes increased their immune response as did high glucose concentrations in the nonblood-fed group. These data indicate that C-25 Sephadex beads can estimate the general strength of An. gambiae’s immune response. However, C-25 beads do not accurately model An. gambiae’s susceptibility to P. falciparum oocysts in natural populations. To the best of our knowledge, this is the first report of field refractoriness in An. gambiae s.l.