In vivo and in vitro experiments showed that human serum albumin (HSA) co-precipitated with components of the commonly used yeast peptone dextrose (YPD) growth medium in aqueous solutions at pH <5. Yeast extract was found to be the primary component of YPD responsible for HSA precipitation. Among yeast extract constituents, RNAs are likely to be most important for HSA precipitation. HSA precipitation at pH <5 was reversible, so that HSA was easily re-solubilized by increasing pH above 6 with completely retained immunoreactivity. The co-precipitation and re-solubilization of HSA were solely pH-dependent and occurred almost instantly at room temperature. Practical aspects of the observed HSA co-precipitation are discussed. (C) 2010 Elsevier Inc. All rights reserved.