The effects of glycine (GLY), D-serine (D-SER), kynurenic acid (KYN), and 7-Cl kynurenic acid (7-Cl KYN), on the evoked release of endogenous norepinephrine (NE) by L-glutamate (L-GLU) in rat hypothalamic slices was investigated. KYN (500 and 100 microM) and 7-Cl KYN (10 microM) blocked evoked release of NE by L-GLU (1 mM). The inhibitory effects of 100 microM KYN on evoked release of NE by L-GLU were reversed by 10 microM and 100 microM D-SER and, but not 10 or 100 microM GLY. When KYN was not present in the superfusate, superfusion with either 10 or 100 microM GLY alone simultaneously with 1 mM L-GLU blocked the evoked release of NE produced by L-GLU. The addition of strychnine (3 or 100 microM) to the superfusate did not block the inhibitory effects of 10 microM GLY on L-GLU-evoked NE release. These findings suggest that a novel strychnine-resistant GLY receptor is present in the rat hypothalamus.