Pimelea species (or desert riceflower) are small native plants endemic to the drier inland pastoral regions of Australia, which cause a unique syndrome in grazing cattle characterized by submandibular edema and edema in the brisket area as a result of right-sided heart failure attributed to the toxin simplexin, 1. Field evidence suggests that poisoning can occur through minor, inadvertent consumption of Pimelea plant material, but the minimum simplexin intake required to induce Pimelea poisoning is not known. In this study, mild Pimelea poisoning was induced at a daily dose of 12.5 mg Pimelea/kg body weight per day, equivalent to 2.5 μg simplexin/kg body weight per day, demonstrating the high potential toxicity of these plant species. Effects in all animals diminished with prolonged low-dose feeding, and it is postulated that these animals developed mechanisms for detoxifying simplexin, 1, possibly through rumen microbial adaptation or activation of liver enzymes.