The tachykinin receptor antagonists (3aR,7aR)-7,7-diphenyl-2(1-imino-2-(2-methoxyphenyl/ethyl)++ +perhydroisoindole) (RP 67580) and (+)-(2S-3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994), which act selectively at neurokinin (NK)1 receptors, inhibited the early phase of formalin-induced pain in mice. Although (+)-(1-hydroxy-3-aminopyrrolidine-2-one) ((+)-HA966), a partial agonist at glycine B receptors, was inactive alone, it potentiated the actions of RP 67580 (but not its inactive stereoisomer, RP68651) and CP-99,994. In its presence, the dose-response curve for RP 67580 was dose-dependently shifted to the left. In contrast, (+)-HA966 did not modify the induction of ataxia by RP 67580 and CP-99,994. These data suggest that co-administration of partial agonists at glycine B receptors may improve the antinociceptive potency and 'therapeutic window' of tachykinin NK1 receptor antagonists.