Release of endogenous cannabinoids decreases excitatory and inhibitory neurotransmission in several brain regions via activation of presynaptic type 1 cannabinoid receptors (CB1 receptors). Activation of group I metabotropic glutamate (mGlu) receptors is known to elicit release of these compounds and in the rodent hippocampus activation of group I mGlu receptors elicits a depression of excitatory synaptic transmission. Thus we were interested to see whether mGlu-receptor-mediated synaptic depression involves the release endocannabinoids which then act as retrograde messengers to stimulate CB1 receptors. Standard in vitro extracellular recordings of fEPSPs were made from area CA1 of hippocampal slices prepared from female Wistar rats (10-13 weeks of age). Rats were killed in accordance with the UK Animals (Scientific Procedures) Act, 1986. Application of the group I mGluR agonist DHPG (100 µM) elicited an acute decrease in fEPSPs to 40 ± 8 % of control (mean ± S.E.M.; n = 8) that reversed only partially upon washout of DHPG (responses 60 min after washout of DHPG were 79 ± 7 % of control; P < 0.05, Student’s paired t test). Delivery of a low-frequency train of paired-pulse stimuli (PP-LFS; 900 paired stimuli at 1 Hz, inter-pulse interval 50 ms) induced a long-term depression (LTD) of synaptic transmission (responses 60 min after delivery of PP-LFS were 80 ± 4 % of control; n = 4; P < 0.05), which is known to be dependent upon activation of group I mGlu receptors. However, neither DHPG-induced depression nor LTD induced by PP-LFS was prevented by application of the CB1 receptor antagonist AM251 (500 nM). In the presence of AM251, DHPG depressed fEPSPs to 68 ± 13 % of control (n = 4; P > 0.05 compared with depression obtained in the absence of AM251, Student’s unpaired t test), and 60 min after washout of DHPG responses were 84 ± 5 % of control. PP-LFS in the presence of AM251 resulted in a reduction of fEPSPs to 81 ± 4 % of control (n = 4; P > 0.05). Thus it appears that release of endocannabinoids and subsequent activation of CB1 receptors is not involved in the induction of these forms of mGlu receptor-dependent depression in the adult rat hippocampus. If, as has been postulated, activation of postsynaptic group I mGlu receptors produces a presynaptic depression in glutamate release, then some other form of retrograde messenger must be involved.