Biomonitoring was used to assess the combined dermal, oral, and inhalation exposure associated with the agricultural use of Harness Plus, an emulsifiable concentrate formulation of the herbicide acetochlor. Twenty Spanish farmers handled and applied acetochlor to maize in the spring of 2003, following the product label recommendations. Open- and closed-cabin applications were equally represented. Urine was collected during six consecutive days, starting the day prior to application. Daily composites were analyzed for 2-ethyl-6-methyl-aniline, a common chemophore representing the major urinary acetochlor metabolites. All applicators showed detectable concentrations in urine after application. Although, the open-cabin applicators treated fewer hectares, they showed significantly higher exposure compared to the closed-cabin applicators (average exposure: 0.004 and 0.002 mg/kg bw/day, respectively). Linear regression analysis suggested that untracked incidents had a significant impact on the total exposure. Other events that may have contributed to the observed exposure are repair of faulty equipment, accidental spillages, splashes, and inadequate use of protective gloves. The average margins of exposure (MOE) for farmers ranged from 23,000 (open cabin) to about 44,000 (closed cabin). For professional applicators the MOEs were 10-fold lower. These MOEs clearly indicate that no adverse health effects should be expected from agricultural acetochlor applications.