Owing to the spread of pyrethroid resistance in Anopheles gambiae s.s. (Diptera: Culicidae) and other vector mosquitoes, there is an urgent need to develop alternative insecticides to supplement the pyrethroids for malaria control. Indoxacarb is an oxadiazine insecticide initially commercialized by DuPont for control of agricultural pests. Performance against An. gambiae bearing kdr (pyrethroid and DDT resistance) or Ace-1R insensitive acetylcholinesterase (organophosphate and carbamate resistance) mechanisms was studied using larval and adult bioassays and a simulated experimental hut system (tunnel tests) that allows fuller expression of the behavioral responses to insecticide. Larval and adult bioassays (topical application and cone tests on treated netting) showed a standard probit dosage-mortality response and no evidence of cross-resistance to the kdr and Ace-1R resistance mechanisms. Toxic activity was slow compared with standard insecticides and additional mortality was observed. Indoxacarb induced no excitorepellency in adults. In tunnel tests, indoxacarb induced no inhibition of mosquito penetration or blood feeding through the holed netting, but it induced delayed mortality over 24-96 h. There was > 90% mortality of the kdr strain on netting treated with the 500 mg/m2 dosage, whereas permethin at 500 mg/nm2 only killed 30% of this strain. A mixture of indoxacarb and pyrethroid showed neither synergism nor antagonism. The absence of cross-resistance to current insecticides indicates that indoxacarb has malaria vector control potential as larvicide or adulticide where mosquitoes are pyrethroid resistant.