The Colorado River shows low levels of perchlorate derived from aerospace- and defense-related fuel industries once located near the Las Vegas Wash. At sufficiently high dosages perchlorate can disrupt thyroid function by inhibiting uptake of iodide. The Colorado River is the primary source of irrigation water for most food crops grown in Southern California and Southwestern Arizona. The objective of this study was to evaluate potential perchlorate exposure from food crops produced in the lower Colorado River region (LCRR). The major food commodities produced in the region were sampled and perchlorate levels were determined by ion chromatography followed by detection using either conductivity or tandem mass spectrometry, depending on analyte levels. The Monte Carlo module of the Dietary Exposure Evaluation Model (DEEM) was used to derive an estimate of the 2-day average perchlorate intakes. Data were derived assuming that individuals residing in the LCRR get their fruits and vegetables from within the LCRR as well as from other areas in the United States, or assuming individuals living in the LCRR get their fruits and vegetables from the LCRR only. Perchlorate exposure estimates derived in this study are comparable to exploratory estimates by the US Food and Drug Administration. For infants and children, over 50% of the estimated perchlorate exposure was from milk. The relative impact of vegetables and fruit toward perchlorate exposure increased by age through adulthood. Cumulative perchlorate exposure estimates based on this hypothetical analysis could approach or exceed the NAS reference dose (RfD) for some population groups as drinking water levels exceeded 6 microg/l. However, few individuals are exposed to perchlorate in drinking water at levels above 4 microg/l in the United States and very few would be exposed to perchlorate levels exceeding the RfD, whether consuming food crops from within or outside the LCRR.