The effects of the strychnine-insensitive glycine receptor antagonists, cycloleucine and 7-chlorokynurenic acid, on the induction of long-term potentiation (LTP) in CA1 of rat hippocampal slices were examined. A 5 min administration of cycloleucine (20-100 microM) or 7-chlorokynurenic acid (1-5 microM) during the delivery of high-frequency stimulation blocked the induction of LTP without affecting baseline synaptic transmission. Coapplication of 100 microM glycine with cycloleucine or 7-chlorokynurenic acid masked the inhibitory effect on the induction of LTP, supporting the hypothesis that these compounds act as glycine antagonists. These results indicate that glycine is a necessary factor for the induction of LTP in CA1 of the rat hippocampus.