Focused-beam microwave irradiation (FBMI) is a relatively new method for euthanasia of small mammals and is available to most researchers. Compared with CO₂ inhalation, this method of euthanasia has the advantage of preserving fast-degrading metabolites. But differences in brain RNA quantity and quality, gene expression and histology in mice euthanized by CO₂ inhalation versus FBMI have not been investigated. Here the authors report that a smaller quantity of RNA was isolated from brains of mice euthanized by FBMI compared with those of mice euthanized by CO₂ inhalation. They also found relative differences in the levels of the expression of some genes. These studies suggest that either method can be used for histological analysis or RNA isolation, but the authors caution against combining the techniques within a single study on gene expression.