The L35 strain of Anopheles gambiae Giles was genetically selected for its ability to melanize and kill malaria parasites. A wide range of Plasmodium species are subject to this response when orally ingested, including the rodent malaria, P. berghei. However, when we directly injected P. berghei into the hemocoel, we found that parasites developed normally to the oocyst stage. This work suggests that the parasite melanization response depends on the interaction of the ookinetes and the midgut. This result is surprising because it contrasts with a genetically validated model system, where injection of CM-Sephadex beads directly into the hemocoel results in bead melanization.