The goal of the present study was to identify sites in the medulla oblongata where metabotropic glutamate receptors are involved in regulating respiration. Unilateral microinjections (50 nl) of L-glutamate (L-glu) (10-25-50 mM) into the nucleus tractus solitarii (NTS) of anaesthetized rats elicited apnea (8.6 +/- 0.3 sec; 21.3 +/- 3.6 sec; 66.3 +/- 16.5 sec respectively; N = 6) and arterial hypotension (7.3 +/- 2.4 mmHg; 10.1 +/- 2.3 mmHg; 35.3 +/- 7.5 mmHg respectively; N = 6). Similarly, in other rats 1-aminocyclopentane-1, 3-dicarboxylic acid (ACPD) (1-5-10 mM), a selective agonist of metabotrophic glutamate receptors, also induced apnea (22.4 +/- 2.5 sec; 32.5 +/- sec; 92.5 +/- 1.4 sec respectively; N = 6) and arterial hypotension (12.7 +/- 2.2 mmHg; 19.6 +/- 4.3 mmHg; 26.5 +/- 1.5 mmHg respectively; N = 6). Paired experiments showed that unilateral microinjections of L-glu (50 mM) and ACPD (1 mM) into the nucleus retroambigualis (NRA) of anaesthetized rats elicited apnea (20.2 +/- 2.6 sec and 33.8 +/- 3.2 sec respectively; N = 6) and arterial hypotension (15.7 +/- 3.7 mmHg and 22.5 +/- 4.5 mmHg respectively; N = 6). The ACPD effects on apnea and hypotension in NTS and NRA were not prevented by a 3 min pretreatment with L-AP3 (30 mM), a putative antagonist of metabotropic glutamate receptors (19.5 +/- 1.4 sec; 12.3 +/- 3.2 mmHg and 30.6 +/- 2.9 sec; 23.4 +/- 3.8 mmHg respectively; N = 6). These data suggest that metabotropic glutamate receptors are involved in NTS and NRA regulation of cardiorespiratory functions.(ABSTRACT TRUNCATED AT 250 WORDS)