The locoweeds, woolly loco and silky crazyweed, contribute to livestock poisoning in the western United States. Differences in response of these two locoweeds to foliar-applied picloram and metsulfuron was investigated by evaluating differences in herbicide uptake, translocation, and metabolism. Silky crazyweed compared to woolly loco was more than 10 times as sensitive to increasing rates of either herbicide. The two species absorbed 8 to 15%, and 11 to 17% of applied picloram and metsulfuron, respectively. Translocation of picloram and metsulfuron out of treated leaflets of either species was less than 3% of that absorbed after 96 h. Approximately 70 and 100% of the absorbed herbicides remained as picloram and metsulfuron, respectively, in both species. Therefore, differences in picloram or metsulfuron uptake, translocation, and metabolism appear inadequate to account for the differential response to each herbicide by the two locoweed species. Selectivity differences between these locoweed genera to picloram and metsulfuron most likely are due to sensitivity differences at sites of action.