Ronald Evans and colleagues at the Salk Institute (La Jolla, CA) report the first transgenic mouse that can sense and react metabolically to human toxins (Nature 406, 435–439, 2000). Animal species respond differently to foreign substances, an observation that prompted the researchers to identify species-specific receptors for xenobiotic sensing mechanisms. Previously, the researchers identified SXR, a human nuclear receptor that responds to xenobiotic compounds by activating cytochrome CYP3A gene expression, leading to toxin degradation. Hypothesizing that evolutionary divergence of this receptor could be responsible for species-specific xenobiotic sensing, they generated mice with a targeted disruption in the mouse homolog, PXR, and showed they could no longer activate CYP3A gene expression in response to rodent-specific CYP3A inducers. Next they introduced an activated form of the human SXR gene into the PXR-null background, and showed that the mice could now sense and degrade human xenobiotics to which rodents are naturally susceptible. Evans believes that the model could be used to screen drugs for spurious activation of SXR, leading to drug–drug interaction. “Antibiotics and even herbal remedies such as St. John's Wort can trigger SXR,” asserts Evans, “and cause women taking oral contraceptives to deliver ‘miracle babies’.”