The effects of halothane, isoflurane and enflurane were compared on three CNS excitatory synaptic pathways in vitro, to determine whether selective actions described in vivo result from differential effects on anatomically distinct cortical pathways and neurone populations. Halothane (0.25-1.25 vol%) depressed postsynaptic excitability of CA1 pyramidal neurones in response to activation of stratum radiatum synaptic inputs, and concentration-dependent excitatory (0.25-1.25 vol%) and depressant (1.5-2.0 vol%) actions were observed on dentate granule neurone excitability and perforant path evoked synaptic responses. In contrast, isoflurane increased CA1 neurone excitability (0.25-0.75 vol%) and produced postsynaptic depression of dentate neurones (0.5-4.0 vol%). Enflurane also increased CA1 excitability (0.5-4.0 vol%), but depressed synaptic responses at equivalent concentrations, and produced mixed excitatory (0.25-1.0 vol%) and depressant (1.0-4.0 vol%) effects on dentate synaptic responses. Differential actions were also observed for the three anaesthetics on stratum oriens excitatory inputs to CA1 neurones, and on antidromic responses. A good correlation (r = 0.992) exists between the membrane/buffer partition coefficients of these anaesthetics and their half-maximal concentrations for depression of synaptic responses; however, this correlation does not reflect the different, anaesthetic-specific actions observed. The results indicate that inhalation anaesthetics act at multiple and selective hydrophobic recognition sites which are heterogenously distributed on different synaptic pathways.