The glycoprotein and ganglioside precursors D-galactosamine and D-glucosamine were tested for effects on acquisition and retention of a brightness discrimination reaction in rats. Intraperitoneally (1.85 mmoles/kg) and intraventricularly (0.8 mumoles) applied D-galactosamine had no influence on acquisition, but improved the retention performance. Intraperitoneally (6.0 mmoles/kg) and intraventricularly (2.4 mumoles) applied D-glucosamine showed qualitatively identical results, i.e. improving effect on retention performance. The penetration abilities of [3H]D-glucosamine and [3H]N-acetyl-D-glucosamine to cross the blood-brain barrier were tested: D-glucosamine penetrated easily the blood-brain barrier (approximately 2:1 relation). However, after intravenous application of 200 mumoles 30 min before training both substances showed a positive effect on retention performance. The findings are discussed in the light that the retention-improving effects of the hexosamines under investigation are believed to be due to a direct, activating influence on glycoprotein and/or ganglioside syntheses in the brain.