The effect of orotic acid and central stimulants on retention of shuttle-box avoidance was investigated in rats. Orotic acid (100 mg/kg) was injected 30 min before training; caffeine (20mg/kg), strychnine (1 mg/kg), or methylphenidate (10 mg/kg) were injected immediately after training. When given alone, these drugs improved avoidance retention when tested 24 h after training. However, improvement of retention was much more evident when orotic acid was given in combination with a stimulant. The data are discussed in relation to the role of macromolecule synthesis and arousal in memory formation.