Maize production in sub-Saharan Africa is limited by its susceptibility to drought and the parasitic weed Striga (Striga asiatica and S. hermonthica). Significant gains have been made in maize breeding under the unique abiotic environmental stresses of sub-Saharan Africa, but maize improved for Striga resistance has lagged behind. There is a paucity of Striga-resistant genes in maize. The potential for broad and durable resistance to the parasite from natural sources is perhaps unlikely in a crop domesticated in the Americas, free from evolutionary Striga pressure. The proposed research explores the possibility of using the emerging technology of RNA interference (RNAi) to enhance this resistance. In this approach, the transgenic maize will produce double-stranded RNA molecules (dsRNA) targeted against genes essential for Striga survival. As Striga establishes on the maize roots, the silencing agent could spread to its cells, shutting down the targeted essential genes and thereby killing the parasite. The Striga genes chosen as targets for the dsRNA interference constructs are either known herbicide targets such as EPSP synthase (5-enolpyruvylshikimate-3-phosphate synthase, target of glyphosate) and ACCase (acetyl-coenzyme carboxylase, cyclohexenones target), or essential plant genes such as AdSS (adenylosuccinate synthetase, the first enzyme in adenosine monophosphate biosynthesis), or VCL1 (vacuoleless1), a gene required for vacuole formation and morphogenesis. RNA was isolated from S. asiatica leaf and root material collected from a Striga-infested maize field. Reverse-transcribed DNA (cDNA) of the target genes was cloned and dsRNA constructs were made and cloned into Syngenta’s maize transformation vectors. Several single-copy maize transgenic events were selected for each dsRNA construct and seeds for each line were produced. Transgenic maize lines thus derived will be tested for Striga resistance at Purdue’s Parasitic Weed Containment Facility. Roots of young maize seedlings will be exposed to pregerminated Striga asiatica under laboratory conditions favouring parasitic attachment. In a series of experiments, individual attached Striga will be monitored over 3–4 weeks in terms of developmental stage reached and vigour. Histological examination of Striga attachments on transgenic maize seedlings will be compared to non-transgenic controls. Message levels of targeted Striga transcripts will also be compared by RT-PCR (polymerase chain reaction). Any transgenic lines effective against S. asiatica will also be tested for resistance to S. hermonthica in the laboratory. Even if the transgenic maize of this study does not effectively block establishment of parasitic Striga, the information it will provide in these studies should allow us to predict if this approach may work using other constructs or in other crop–parasitic weed associations. If these RNAi constructs result in Striga-resistant maize, they should also work in other cereals such as sorghum or millet and could eventually be engineered into those crops.