In mammals, general anaesthetics are thought to operate by activating endogenous sleep mechanisms, but whether similar mechanisms operate in flies is not understood. Genetically enhancing levels of synaptic activity in neurons of the dorsal fan-shaped body of the central complex increased sensitivity to the general anaesthetic isoflurane (ISO), but increasing transmitter release in specific wake-promoting dopaminergic neurons conferred ISO resistance. These findings reveal common pathways for sleep and the action of general anaesthetics in the fly brain.