BACKGROUND: Evolution of insecticide resistance in Anopheles gambiae complex necessitates evaluation of alternative chemical classes to complement existing insecticides for long lasting insecticidal nets (LLIN) and indoor residual spraying (IRS). Microencapsulated (MC) DEET (N, N-diethyl-m-toluamide) is a formulation of the popular repellent, which gives long lasting activity when applied to nets. Its suitability for IRS use has not been evaluated before. This study assessed the efficacy of DEET MC, for IRS in experimental huts. METHODS: DEET MC was tested alongside standard repellent and non-repellent residual insecticides: lambdacyhalothrin, permethrin, pirimiphos methyl and DDT. Residual formulations of these compounds were sprayed on plywood panels attached to walls of experimental huts to assess efficacy against pyrethroid resistant, wild free-flying Anopheles arabiensis and Culex quinquefasciatus. The panel treatments were rotated weekly between huts. RESULTS: The overall mortalities of An. arabiensis induced by the various treatments (range: 76-86%) were significantly greater than mortality in the untreated control (8%, P < 0.001). Mortality of An. arabiensis in DEET sprayed huts (82%) was higher than in lambdacyhalothrin CS (76%, P = 0.043) but not significantly different to pirimiphos methyl CS (86%, P = 0.204) or DDT huts (81%, P = 0.703). Against Cx. quinquefasciatus DEET MC was less effective, inducing lower mortality (29%) than other treatments. An arabiensis blood feeding rates were higher in the unsprayed control (34%) than in sprayed huts (range between treatments: 19-22%, P < 0.002), and DEET provided equivalent or superior blood feeding inhibition (44%) to other insecticides. Against Cx. quinquefasciatus there was no significant reduction in blood-feeding for any treatment relative to the control. There was a significantly higher exiting of An. arabiensis from huts sprayed with DEET (98%), lambdacyhalothrin (98%) and permethrin (96%) relative to the control (80%, P < 0.01). Exiting rates of Cx. quinquefasciatus did not differ between treatment huts and the control. CONCLUSION: Microencapsulated DEET acts like an insecticide at ambient temperature and induces mosquito mortality when applied to walls made from wooden panels. This trial demonstrated the potential of microencapsulated DEET to control An. arabiensis and warrants further studies of residual activity on interior substrates.