1. Investigation with substances that are similar in structure, but different in anaesthetic properties, may lead to further understanding of the mechanisms of general anaesthesia. 2. We have studied the effects of two cyclobutane derivatives, the anaesthetic, 1-chloro-1,2,2-trifluorocyclobutane (F3), and the non-anaesthetic, 1,2-dichlorohexafluorocyclobutane (F6), on K+-evoked glutamate and gamma-aminobutyric acid (GABA) release from isolated, superfused, cerebrocortical slices from mice, by use of h.p.l.c. with fluorescence detection for quantitative analysis. 3. At clinically relevant concentrations, the anaesthetic, F3, inhibited 40 mM K+-evoked glutamate and GABA release by 72% and 47%, respectively, whereas the structurally similar non-anaesthetic, F6, suppressed evoked glutamate release by 70% but had no significant effects on evoked GABA release. A second exposure to 40 mM KCl after a approximately 30 min washout of F3 or F6 showed recovery of K+-evoked release, suggesting that F3 and F6 did not cause any non-specific or irreversible changes in the brain slices. 4. Our findings suggest that suppression of excitatory neurotransmitter release may not be directly relevant to the primary action of general anaesthetics. A mechanism involving inhibitory postsynaptic action is implicated, in which a moderate suppression of depolarization-evoked GABA release by the anaesthetic may be consistent with the enhancement of postsynaptic GABAergic activities.