A refractory strain of the mosquito, Anopheles gambiae, melanotically encapsulates and destroys malaria parasites in the midgut. Normal development of parasites is observed in a closely related susceptible strain. To examine the basis for the difference in response, the two strains were compared for responses to inoculated Sephadex beads of varying charge. Negatively charged C-25 beads elicited a much stronger reaction in the refractory strain where 49% of the beads were strongly melanized by 24 h, compared with only 5% in the susceptible strain. Male mosquitoes of each strain responded similarly, with 100% of the beads strongly melanized by 24 h in the refractory strain compared with only 5% in the susceptible strain males. A time course revealed that the melanization in refractory but not susceptible mosquitoes increases substantially over time; 91% of C-25 beads were melanized in refractory females at 72 h compared with 9% in the susceptible sample. Neutral G-25 beads and positively charged A-25 beads were melanized in both strains, demonstrating that the capacity to melanize foreign particles is present in susceptible mosquitoes.