Technical Abstract: Objective-This study tested the hypothesis that a Delphinium occidentale chemotype containing the MSAL-type alkaloids is more toxic than a D. occidentale chemotype lacking the MSAL-type alkaloids in mice and cattle. Animals-240 male Swiss Webster mice and 11 black Angus steers Procedures-Total alkaloid extracts from eight plant collections were administered by tail vein injection to male Swiss Webster mice. Dried, finely ground larkspur was administered to steers by oral gavage in a range of doses equivalent to 37.6-150.4 mg/kg body weight of total alkaloids. The steers were monitored for heart rate at time zero and 24 hours. The steers were exercised as a measure of muscle weakness. Results-Alkaloid extracts prepared from plant populations containing the MSAL-type alkaloids had an average LD50 in mice of 2.3 mg/kg BW versus 54.2 mg/ kg BW from extracts prepared from plant populations lacking the MSAL-type alkaloids. A similar trend was observed in cattle as the steers responded differentially in terms of heart rate and muscle weakness to larkspur due to the presence or absence of the MSAL-type alkaloids. Conclusions and Clinical Relevance-D. occidentale containing the MSAL-type alkaloids poses a distinct quantifiable risk of being toxic to livestock. Alternatively, D. occidentale containing only the MDL-type alkaloids is much less toxic, and the corresponding risk to grazing livestock appears to be lower. Further research in cattle will be necessary in order to refine grazing management recommendations when larkspur with these chemotypes is present on rangelands.