The linkage between agonist binding and the activation of a GABA_A receptor ion channel is yet to be resolved. This aspect were examined on human recombinant 122S GABA_A receptors expressed in human embryonic kidney cells using the following series of receptor agonists: GABA, isoguvacine, 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP), isonipecotic acid, piperidine-4-sulphonic acid (P4S), imidazole-4-acetic acid (IAA), 5-(4-piperidyl)-3-isothiazolol (thio-4-PIOL), and 5-(4-piperidyl)-3-isoxazolol (4-PIOL). Whole-cell concentration-response curves enabled the agonists to be categorised into four classes based upon their maximum responses. Single channel analyses revealed that the channel conductance of 25-27pS was unaffected by the agonists. However, two open states were resolved from the open period distributions with mean open times reduced 5-fold by the weakest partial agonists. Using saturating agonist concentrations, estimates of the channel shutting rate, , ranged from 200 - 600s^-1. The shut period distributions were described by 3 or 4 components and for the weakest partial agonists, the interburst shut periods increased whilst the mean burst durations and longest burst lengths were reduced relative to the full agonists. From the burst analyses, the opening rates for channel activation, , and the total dissociation rates, k_-1, for the agonists leaving the receptor were estimated. The agonist efficacies were larger for the full agonists (E 7-9) compared to the weak partial agonists ( 0.4-0.6). Overall, changes in agonist efficacy largely determined the different agonist profiles with contributions from the agonist affinities. From this we conclude that GABA_A receptor activation does not occur in a switch-like manner since the agonist recognition sites are flexible, accommodating diverse agonist structures which differentially influence the opening and shutting rates of the ion channel.