Concern about false negative serology tests for infectious diseases in hemodiluted cadaver donors resulted in issuance of new regulations and guidelines from the FDA and CDC. Bone or tissue from donors receiving > or = 4 units of blood, blood products, colloids or crystalloids within 48 h of sampling must be quarantined unless: (a) a pretransfusion serum is available; or (b) an adequate algorithm is employed to ensure hemodilution is insufficient to alter test results, i.e. cause false negatives. Left undefined in these regulations is, what is an adequate algorithm and what amount of hemodilution would cause false negatives. A pretransfusion sample was not available for about 20% of our donors and many had incomplete infusion histories. We used the unambiguous quantitation of serum albumin and total protein to define hemodilution and, if present, hemoconcentration of sera by ultrafiltration to normal protein levels prior to serology testing. Control experiments showed excellent correlation between serum dilution and protein concentration (r > 0.99) and a quantitative recovery of 96.9 +/- 1.4% upon hemoconcentration. Known positive sera (CMV-Ab; HTLV-1Ab; HIV-1,2Ab; HBsAb; HCV-Ab; HBsAg) were spiked into normal sera and diluted up to 1:2000, well beyond detectable levels. A qualitative recovery of 100% and a quantitative recovery of 97.6 +/- 7.5% of antibody or antigen reactivity was achieved upon hemoconcentration and retesting. In two studies, 14% (30/210) and 43% (23/54) of cadaver donors had serum proteins below normal limits and their sera was hemoconcentrated.(ABSTRACT TRUNCATED AT 250 WORDS)