We have recently reported a new protocol for inducing long-term depression through activation of GABAA receptors in the hippocampal site. This long-term depression is reversed by bicuculline and potentiated by neurosteroids such as alphaxalone and 5 alpha-pregnan-3 alpha-ol-20-one. It was also shown that glutamate receptor activity is not involved in the induction of this type of long-term depression. The present study investigates the role of calcium in the induction of this novel form of long-term depression and attempts to determine the mechanism of reversal of muscimol-induced long-term depression. Extracellular recordings were made in the CA1 pyramidal cell layer of rat hippocampal slices following orthodromic stimulation of Schaffer collateral fibres in stratum radiatum (0.01 Hz). It was observed that the muscimol-induced long-term depression can be obtained in the absence of calcium in the bathing medium. In addition to this, the long-term depression was reversed by N-methyl-D-aspartate, kainic acid, high potassium medium, veratrine and the calcium ionophore A23187 but not high calcium (10 mM) medium. High potassium medium in the absence of calcium reversed the long-term depression induced by muscimol 10 microM. The results suggest that this type of glutamate-independent long-term depression can be induced in the absence of extracellular calcium. Extracellular calcium is not necessary for reversal of the long-term depression, although when intracellular calcium levels are raised, as by A23187, this is capable of inducing reversal.