Sleep is an essential resting status and sleep deprivation is lethal. An important step in sleep generation is inhibition of the wake-promoting neurons regular firing by GABA. The GABAA receptor (GABAAR) is a target for sedative pharmacotherapy. Behavioural studies on mice with deleted or mutated GABAAR subunits indicated that GABAARs expressed in the hypothalamus, which contain alpha 2 or/and beta 3 subunits are most important for sleep regulation. Neurons were isolated from two major waking centres in the posterior hypothalamus of rats: histaminergic neurons from the tuberomamillary nucleus and orexinergic neurons from the perifornical area. They were investigated using whole-cell recordings combined with single cell RT-PCR for 13 subunits of the GABAAR. Pharmacological characterization indicates 3 overlapping but not identical functional areas responsible for GABAAR heterogeneity: i) sensitivity to GABA (EC50s vary from 2 to 60mM, determined by gamma subunits expression), ii) propofol resistance (determined by the epsilon subunit expression), iii) expression of constitutively active GABAARs of unknown composition. Further heterogeneity areas are under current investigation. Their relation to sleep and anaesthesia will be discussed.