The respiratory role of group I and II metabotropic glutamate receptors (mGluRs) was investigated in the in vitro lamprey brainstem preparation by analysing changes in respiratory activity induced by bath application of specific agonists (10 and 25 micro m) and antagonists (500 micro m). Respiratory responses reached their maximum within 10 or 15 min, without any obvious further changes during application periods of 60 min The broad-spectrum mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) and the specific group I mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) caused dose-dependent increases in respiratory frequency and peak vagal activity. DHPG at higher concentrations (50-100 micro m) did not cause any further consistent change in respiratory variables. Two different agonists acting on group II mGluRs, i.e. (2S,3S,4S)-CCG/(2S,1'S,2'S)-2-(carboxycyclopropyl)-glycine (L-CCG-I) and (2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG-IV), were employed. At 10 micro m DCG-IV increased respiratory frequency, whilst L-CCG-I did not produce any significant effect. Both drugs increased respiratory frequency and peak vagal amplitude at 25 micro m. The nonselective group I and II antagonist (S)-alpha-methyl-4-carboxyphenylglycine (MCPG) as well as the specific group I antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) elicited reversible reductions in respiratory frequency. Blockade of group II mGluRs by (2S)-alpha-ethylglutamic acid (EGLU) increased both frequency and peak amplitude of vagal bursts. The results indicate that both group I and II mGluRs have an important modulatory role in the control of the lamprey pattern of breathing, probably through an action on the rhythm generating mechanisms. They support the view that these receptors are activated under physiological conditions and differentially affect the frequency and intensity of respiratory bursts.