With the exception of a few strains such as BuB/BnJ, complement activity in most inbred strains of mice is remarkably similar. The BuB/BnJ strain reportedly has high levels of complement activity and elevated serum levels of C3 and other complement proteins. However, we observed that BuB/BnJ mice have serum C3 levels comparable to those seen in C57BL/6, Balb/c and several other strains of inbred mice. More importantly, using bacteria as a substrate for activation and deposition of complement as a direct biological assay to assess serum complement opsonic activity, we found that BuB/BnJ mice do not have elevated complement activity compared to other inbred mouse strains. In contrast hemolytic assays indicate BuB/BnJ sera to be most active. These results indicate that accepted views regarding mouse serum complement activity need to be re-examined. © 2005 Elsevier Ltd. All rights reserved.