The Colorado River is contaminated with perchlorate concentrations of 1.5-8 microgram/L, an anion linked to thyroid dysfunction. Over 90% of the lettuce (Lactuca sativa L.) consumed during the winter months in the United States is produced in the Lower Colorado River region. Studies were conducted in this region to survey the potential for lettuce perchlorate accumulation and estimate potential human exposure to perchlorate from lettuce. Total uptake of perchlorate in the above-ground plant of iceberg lettuce was approximately 5 g/ha. Exposure estimates ranged from 0.45 to 1.8 microgram/day depending on lettuce types and trimming. For all lettuce types, hypothetical exposures were less than 4% of the reference dose recommended by the National Academy of Sciences. Results show the relative iodide uptake inhibition potential because of lettuce nitrate was 2 orders of magnitude greater than that associated with the corresponding trace levels of perchlorate. These data support the conclusion that potential perchlorate exposures from lettuce irrigated with Colorado River water are negligible relative to acute or long-term harmful amounts.