A series of 7-(2-hydroxyethyl)benz[e]indene analogues of 3α-hydroxy-5β-pregnan-20-one (7), a neuroactive steroid known to be a positive allosteric modulator of GABAA receptor function, was prepared. Electrophysiological measurements carried out on cultured rat hippocampal neurons were used to evaluate the modulatory effects of the analogues on GABAA receptor function. Analogues were tested for their ability to potentiate 1 μM GABA-mediated chloride currents and for their ability to directly gate chloride currents at this ligand-gated ion channel. Active analogues typically enhanced GABA-mediated currents at concentrations below those required to directly gate chloride currents. The dose-response relationships for potentiation of 1 μM GABA-mediated chloride currents were studied for [3S-(3α,3aα,5aβ,7β,9aα,9bβ)]-1-[dodecahydro-7-(2-hydroxyethyl)-3a-methyl-1H-benz[e]inden-3-yl]ethanone (3), steroid 7, 3α-hydroxy-5α-pregnan-20-one (5), and the analogous 7α-(2-hydroxyethyl)benz[e]indene analogue of steroid 5 (compound 1). Compound 3 was the most active potentiator (EC50 = 0.017 μM) of GABA-mediated current. The direct gating actions of compound 3 were not observed at a concentration of 1 μM, but were observed at a concentration of 10 μM.