The newborn rat brainstem-spinal cord preparation was used to study the effects of tachykinins on the activity of the respiratory rhythm generator in vitro and to characterize the receptors involved. Substance P and tachykinin NK 1 and NK 3 receptor agonists induced a concentration-dependent increase in the respiratory frequency (10 - 9 -10 - 7 M), whereas the respiratory frequency was only slightly affected by the tachykinin NK 2 receptor agonist. Pre-treatments with tachykinin NK 1 receptor antagonists (SR140333, (S)1-{2-[3-(3.4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)piperidin-n-3-yl ]ethyl}-4-phenyl-1-azoniabicyclo[2,2,2]octane chloride; GR82334, pGlu-Ala-Asp-Pro-Asn-Lys-Phe-Tyr-(S-S)Pro-Leu(spiro-γ-lactam)-Trp-NH 2 ) reduced the substance P-induced increases in the respiratory frequency but the tachykinin NK 2 receptor antagonists (SR48968, ((S)-N-methyl-N-[4-(4-acetylamino-4-phenylpiperidine)-2-(3,4-dichlorophenyl) butyl]benzamide); MEN 10376, Asp-Tyr-d-Trp-Val-d-Trp-d-Trp-Lys-NH 2 ) had no effect; the increase in the respiratory frequency induced by the tachykinin NK 3 receptor agonist was not affected by a pre-treatment with tachykinin NK 1 and NK 2 receptor antagonists. These results indicate that tachykinin NK 1 and NK 3 receptors may be involved in the control of the respiratory frequency.