Immunotherapy for Alzheimer’s disease (AD) has been the subject of intense investigation. Both active and passive immunization against-amyloid peptide (A) in mouse models reduce levels of A, prevent and clear amyloid plaques, and improve cognitive behavior (1). We studied passive immunization of APP23 transgenic mice, a model that exhibits the age-related development of amyloid plaques and neurodegeneration as well as cerebral amyloid angiopathy (CAA) sim-ilar to that observed in the human AD brain (2, 3). Consistent with earlier reports, we found that passive A immunization results in a significant reduction of mainly diffuse amyloid. However, it also induces an increase in cerebral microhemorrhages associated with amyloid-laden vessels, suggesting a possible link to the neuroinflammatory complications of A immunization recently seen in a human trial (1). Male 21-month-old APP23 mice (n 10) were passively immunized weekly by intraperitoneal injections of 0.5 mg of 1 mouse monoclonal immunoglobulin G1 antibody that recognizes amino acids 3 to 6 of human A (4). Age-matched APP23 control mice were injected with phosphate-buffered saline (n 11). After 5 months of treatment, stereological analysis of amyloid load (4) revealed a significant amyloid reduction (23%; P 0.0008) in neocortex of the immunized mice compared with controls (Fig. 1, A and B). This reduction was largely accounted for by a reduction (33%; P 0.001) in diffuse amyloid. Enzyme-linked immunosorbent assay measurements of formic acid extracted brain samples (4) showed a significant reduction in A42 (44.8 2.7 and 34.7 3.1 g/g wet weight for control and immunized mice, respectively; P 0.03), but no significant reduction in A40 (166.2 11.3 compared with 152.7 12.2 g/g).