Herbicide contamination of streams has been well documented, but little is currently known about the specific factors affecting watershed vulnerability to herbicide transport. The primary objectives of this study were (1) to document herbicide occurrence and transport from watersheds in the northern Missouri/southern Iowa region; (2) to quantify watershed vulnerability to herbicide transport and relate vulnerability to soil properties; and (3) to compute the contribution of this region to the herbicide load of the Missouri and Mississippi Rivers. Grab samples were collected under baseflow and runoff conditions at 21 hydrologic monitoring stations between April 15 and July 15 from 1996 to 1999. Samples were analyzed for commonly used soil-applied herbicides (atrazine, cyanazine, acetochlor, alachlor, metolachlor, and metribuzin) and four triazine metabolites (deisopropylatrazine, deethylatrazine, hydroxyatrazine, and cyanazine amide). Estimates of herbicide load and relative losses were computed for each watershed. Median parent herbicide losses, as a percentage of applied, ranged from 0.33 to 3.9%; loss rates that were considerably higher than other areas of the United States. Watershed vulnerability to herbicide transport, measured as herbicide load per treated area, showed that the runoff potential of soils was a critical factor affecting herbicide transport. Herbicide transport from these watersheds contributed a disproportionately high amount of the herbicide load to both the Missouri and Mississippi Rivers. Based on these results, this region of the Corn Belt is highly vulnerable to transport of herbicides from fields to streams, and it should be targeted for implementation of management practices designed to reduce herbicide losses in surface runoff.