N-methyl-D-aspartate (NMDA) receptors play an important role in learning and memory. Targeting the glycine modulatory site of the NMDA receptor has been suggested as a therapeutic strategy to improve cognition, although findings have not been convincing. We used the Cognitive Drug Research computerised assessment system to examine the effects of high-dose glycine on a number of cognitive processes in healthy young subjects. The study was a randomised placebo controlled repeated measures design in which each subject received acute placebo or glycine (0.8 g/kg) orally, with treatment conditions separated by a 5-day washout period. No significant effects of glycine were found on measures of working memory, declarative memory, attention or perceptual processing. These findings, together with those of previous studies, cast doubt over the ability of acute high-dose glycine to improve cognitive function in healthy subjects and suggest that the optimum dose of glycine for improving cognition may vary between different populations, possibly due to differences in endogenous glycine levels and the functional status of NMDA receptors.