Activation of group II and III metabotropic glutamate receptors (mGluRs) facilitates spontaneous glutamate release in the entorhinal cortex (EC) 4-6 week old rats (Evans et al. 2000; Ayman et al. 2003). In an accompanying presentation at this meeting (Jones, Ayman & Woodhall) we have shown that this effect of the mGluRs is reversed to depression in older animals (5-6 months). A large body of literature has shown diverse changes in function of mGluRs in animal models of epilepsy. In the present experiments we have looked for adaptive changes in group II and group III mGluR function in the EC of chronically epileptic rats. Male Wistar rats, previously rendered chronically epileptic, were humanely killed and slices of EC were prepared using conventional techniques (Glien et al. 2001) and compared to age-matched control (AMC) animals (5-6 months). At the time of experiments, all epileptic animals were exhibiting spontaneous recurrent seizures. Glutamate release was monitored by recording spontaneous excitatory postsynaptic currents (sEPSCs) from neurones in layer V. All recordings were made in the presence of the NMDA receptor blocker, MK-801 (10 μM), so EPSCs reflect activation of AMPA receptors. Data are expressed as mean±s.e.m. Statistical comparisons were made using either the Wilcoxon rank sum test (WRST) or the Kolmogorov-Smirnov test (KS). In 14 cells from the AMC group mean interevent interval (IEI) was 246.5±6.6 ms, and in 17 cells from the epileptic group mean IEI was slightly less at 220.9±5.1 ms. Mean amplitude of sEPSCs was also slightly larger in the cells from the epileptic group (13.4±0.2 pA v 14.6±0.1 pA). However, neither change was significant (WRST, P>0.1). Many cells from the epileptic group displayed burst-like activity and this was not observed in any cells from the AMC group. In 8 layer V neurones from AMC animals, the group III mGluR agonist, ACPT-1 (20 μM), increased the mean IEI of sEPSCs from 265.7±9.5 ms to 357.3±10.3 ms (KS, P<0.001), reflecting a 28% decrease in frequency. In 9 cells from the epileptic group mean IEI increased from 222.7±6.5 ms to 740.2±204.1 ms (KS; P0.1). In AMC animals the group II agonist, DCG-IV (5 μM), in the presence of CPPG to block group III mGluRs, decreased frequency by approximately 30% (KS, P<0.001), whereas, in neurones from epileptic animals the reduction was over 50%. Thus, the depression of glutamate release by both groups of receptor appears to be enhanced in chronically epileptic animals. This might reflect an adaptive change in an attempt to dampen hyperexcitability in cortical networks.