In this article we develop a calculation or formula for use in determining the potential dilution effect of fluids administered during patient treatment on serologic testing parameters. The formula uses basic principles of (a) fluid distribution over time from administration; (b) ratios of plasma and extravascular fluid volumes to body weight; and (c) common practices of fluid resuscitation. A dilution threshold of 50% was set using data from enzymelinked immunosorbent assay human immunodeficiency virus antibody determinations performed on in vitro diluted seropositive serum samples. These data respond to issues raised by guidelines from the Centers for Disease Control and the U.S. Food and Drug Administration to achieve recipient safety without unnecessarily restricting the potential donor pool.