Abstract Because the cellular effects of β-amyloid protein (β-AP) are currently unclear, we evaluated the in vivo effects of β-AP implants in a lipid matrix to prolong tissue exposure in the brains of rats. Young 3-month-old rats and aged 18-month-old rats received implants of β-AP prepared in a cocoa butter matrix in the dorsal hippocampus and corpus striatum on one side of the brain and implants of either prolactin or scrambled β-AP peptide in cocoa butter on the contralateral side. The old rats also received implants of β-AP embedded in a cholesterol matrix or cholesterol alone in the frontal cortex. The young rats were sacrificed 3–4 days after implantation, while the old rats were sacrificed 6–8 weeks after implantation. Lesion size on the β-AP implanted side did not differ significantly from lesion size observed with control peptides. Bielschowsky silver staining revealed few arygyrophilic neurites and axonal spheroids associated with either β-AP or control implants. Alz 50 and ubuquitin immunoreactivity were not observed. None of the implant sites demonstrated cytopathology characteristic of Alzheimer's disease. The results of this study indicate that β-AP implantation into the brains of rats produced no consistent effect beyond that seen with control peptide implants.