Beta amyloid (22-35) is a synthetic truncated fragment of beta-amyloid peptide. It has been demonstrated that beta amyloid (22-35) possesses a cytotoxic effect on cultured rat hippocampus neurons in serum-free medium. Aggregates and typical amyloid fibrils resembling those of the beta amyloid protein (AP) are formed in neutral buffer solution from beta amyloid (22-35). These fibrils show characteristic staining with Congo red and thioflavin-S. The neurotoxicity of beta amyloid (22-35) can be suppressed by addition of calf serum, dibutyryl cAMP, or insulin to the culture medium. However, the addition of NGF or substance P will not suppress the neurotoxicity. Beta amyloid (22-35) does not act on glial cells. These results suggest that AP can induce neurotoxicity in hippocampal cells in vitro and may result in a disorder involving intracellular signal transduction.