The availability of genetically modified mice has allowed the study of genetic influences on acute brain injury. An animal model of acute subdural hematoma (ASDH) has been previously described in the rat but not the mouse. We describe a method for producing ASDH in the mouse. Subdural injections of 50 and 30 microL of nonheparinized autologous blood were associated with excessive mortality. Injections of 10 and 20 microL were associated with mean percentage volumes of damage of 1.804% and 4.019%, respectively. Sham subdural injections of saline were associated with minimal hemisphere damage (0.152%). This mouse model provides a means of investigating the effects of genotype on the brain's response to ASDH.