Diuron is one of the most heavily used herbicides in California, and well water and surface water are routinely monitored for diuron residues. In a previous paper, we described haptens and monoclonal antibodies suitable for quantitative competition enzyme immunoassay (EIA) of diuron. This paper documents the design and results of a study conducted with 49 blind-coded groundwater samples, analyzed by high-pressure liquid chromatography (HPLC) and EIA. Diuron residues were recovered using a C-18 solid-phase extraction (SPE) protocol that also is applicable to the recovery of simazine, atrazine, prometon, and bromacil. To minimize analyst errors, all SPE and EIA steps were performed on automated equipment. Overall correlation of the EIA and HPLC results was r(2) = 0.95, with a low bias in the EIA (ppb estimated by EIA = 0.77 x ppb estimated by HPLC). The detection limits of the EIA and HPLC were approximately 0.07 and 0.1 ppb, respectively. There were no false positives or false negatives in the EIA. The results indicate that the residue extraction and EIA protocols are suitable for initial screening for compliance monitoring of diuron. The protocols are potentially adaptable to multiresidue screening for leachable herbicides in water samples.