Anopheles stephensi and mammals limit malaria parasite (Plasmodium spp.) infection with the synthesis of nitric oxide (NO). The synthesis of this toxic free radical gas is catalyzed by A. stephensi NO synthase (AsNOS), a transcriptionally complex gene with parasite-inducible expression observed as early as 1h post-infection. In an effort to determine whether AsNOS is a reasonable target for the genetic manipulation of mosquito resistance to parasite development, we have focused on identifying parasite factor(s) that induce AsNOS expression, endogenous and exogenous regulatory factors that refine AsNOS expression, and the potential for self-inflicted or autoimmune-like pathology in the mosquito. Surprisingly, the same parasite factor(s), signaling pathways, regulatory factor(s), and damage control pathways that act in mammalian cells before and during infection-related NO synthesis are shared by A. stephensi. This level of conservation from inducers to effector to regulators is a striking example of conservation of innate immunity in diverged hosts of a single parasite.