Prostate specific antigen (PSA) determinations after radical prostatectomy are valuable in detecting persistent disease. Previously, we determined that 0.4 ng./ml. PSA was a reliable clinical threshold using the Hybritech Tandem-R PSA assay. Recently, we reported that a new PSA immunoassay (Abbott IMx PSA) correlated well with results of the Tandem-R immunoradiometric PSA assay and had a lower threshold. Using a conservative threshold of 0.1 ng./ml. PSA for the IMx PSA assay, we analyzed IMx PSA values in serial postoperative serum from 72 radical prostatectomy patients whose initial Tandem-R levels were less than 0.4 ng./ml. PSA. The lower detection limits of the IMx PSA assay allowed approximately a third (15 of 42) more detection of persistent disease within 8 months of surgery. When the PSA level remained undetectable for more than 8 months but the disease eventually recurred the lead times averaged 9 to 12 months when 0.1 ng./ml. PSA was used to signify persistent disease. All patients whose PSA levels reached 0.1 ng./ml. PSA and were subsequently followed for more than 3 months continued to have increasing levels. Also, every man who eventually had recurrence also had a PSA serum level of at least 0.1 ng./ml. PSA within 28 months postoperatively, although the subsequent increase from 0.1 to 0.4 ng./ml. PSA sometimes took several years. Although the clinical impact of these findings is yet unknown, new or altered PSA assays with lower detection limits can provide unique information that may offer opportunities for improved clinical investigation and possibly patient management.