In the present work, the effect of corticosterone, 3α5α-corticosterone and 3α5β-corticosterone on GABA mediated chloride flux were studied in rat cortical microsacs. All three steroids reduce the chloride ion uptake with a maximum of approximately -30%. The reduction induced by corticosterone and 3α5α-corticosterone showed a concentration-response pattern with IC₅₀ values of 1.6 nM and 1.0 nM respectively. The reducing effect cannot be seen in the absence of GABA. The GABAergic transmission plays a crucial role in pathophysiology of diseases such as anxiety and in mental disorders such as depression, schizophrenia and drugs of abuse. The pathophysiology of these disorders can to some extent be related to changes in neurosteroid levels and thereby to the modulations of GABA_A receptor function. The well-known GABA_A-receptor modulators, allopregnanolone and tetrahydrodeoxycorticosterone, are released during stress and originate from the same branched synthetic pathway as the species-specific glucocorticoid, corticosterone, in rats.