We examined the histological changes produced by injections of beta-amyloid [beta(1-40)], and control peptides in rat and monkey cerebral cortex. beta(25-35) injections were also studied in rat cortex. Standard immunoperoxidase procedures were used to detect the distribution of tau, MAP2, beta(1-40) and ALZ 50 immunoreactivity. All injections produced localized necrosis at the injection site surrounded by a zone of neuronal loss and gliosis. In rat cortex, lesions produced by solubilized beta(1-40) and beta(25-35) in water were generally larger than those produced by control peptides. Tau and ALZ 50 antibodies labeled neurites and diffusely positive perikarya around beta(1-40) injections, whereas MAP2 staining was reduced, paralleling the distribution of neuronal loss and gliosis. In aged primate cortex, beta(1-40) lesion size was dose dependent. Hyalinized, ALZ 50 positive neurons, and abnormal neurites were prominent around the injection site. Although beta-amyloid is acutely neurotoxic in both rat and monkey cerebral cortex, neuronal degeneration in the primate more closely resembles that found in AD.