Administration of drugs activating cannabinoid CB 1 receptors in the brain induces memory deficit in rodents, and blockade of these receptors may restore memory capacity in these animals. Central administration of β-amyloid or β-amyloid fragments may also lead to memory disturbances. This study was undertaken to study the involvement of cannabinoid CB 1 receptors in amnesia induced by β-amyloid fragments in mice tested in a step-through passive avoidance paradigm. Pre-training intracerebroventricular (i.c.v.) injection of β-amyloid fragments, β-amyloid peptide-(25–35) (4, 8 or 16 nmol/mouse) or β-amyloid peptide-(1–42) (200, 400, 800 pmol/mouse) 7 days prior to the learning trial reduced in a dose-dependent manner the retention of passive avoidance response. This effect was observed in two retention tests, 1 and 7 days after the learning trial. The two β-amyloid fragments showed similar potency in reducing retention of passive avoidance behavior. This effect was counteracted by a single intraperitoneal (i.p.) injection of the cannabinoid CB 1 receptor antagonist, N-(piperidin-l-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1 H-pyrazole-3-carboxamide hydrochloride (SR141716A, 1 mg/kg), made 30 min prior to the second retention test. The injection of SR141716A per se did not affect memory capacity of mice. The i.c.v. administration of β-amyloid peptide-(25–35) (8 nmol/mouse) or of β-amyloid peptide-(1–42) (400 pmol/mouse) made 30 min prior to the learning trial failed to affect the retention capacity of mice as measured 1 and 7 days later. Also, the i.p. injection of SR 141716A (1 mg/kg) made 30 min prior to the learning trial did not influence the behavioral response of mice injected with β-amyloid peptide-(25–35) (8 nmol/mouse) or of β-amyloid peptide-(1–42) (400 pmol/mouse) 7 days prior to the learning trial. These results show that β-amyloid fragments induce a dose-dependent memory deficit. Their effect on memory retention depends upon the time of administration and seems to involve cannabinoid CB 1 receptors in the brain.