Microinjections into the dorso-lateral periaqueductal gray (PAG) area of trans-ACPD (6 - 30 nmol/rat), an agonist of group-I and group-II metabotropic (mGlu) receptors, significantly decreased arterial blood pressure (ABP). 1S,3R-ACPD (0.05 - 5 nmol/rat), the active isomer of trans-ACPD, injected in the same area, significantly decreased (0.05 nmol) or increased (5 nmol) ABP. Pretreatment, 5 min before 1S,3R-ACPD, in the same area with (S)-MCPG (30 nmol/rat), a non-selective antagonist of mGlu receptors, was able to prevent both hypotension and hypertension induced by (1S,3R)-ACPD. (S)-MCPG alone did not change ABP. Microinjections of L-SOP (0.05 - 5 nmol/rat), a non-selective agonist of group-III mGlu receptors, resulted scarcely effective in changing ABP; just the higher dose (5 nmol) induced a short and significant increase in ABP. This effect was prevented by (S)-MCPG (30 nmol/rat). These data confirm the complexity of mGlu receptors as well as their multiple roles in the CNS. In particular, as expected from the multiplicity of transduction mechanisms associated with these G-protein-coupled receptors, mGlu receptors in the PAG vasopressor neurons may either modulate an increase or a decrease in ABP. We speculated that group-II mGlu receptors inhibit, while group-I mGlu receptors potentiate, the activity of PAG vasopressor neurons.