Recombinant fully deuterated, defatted human serum albumin in heavy water was found to be about 90% aggregated before final fractionation. For comparison and to establish a datum for this isotope effect, the extent of aggregation is reported for "native" defatted and fatted human serum albumin solutions in phosphate buffered 1 mg/ml in heavy and light water at 25 °C and at 4 °C. The extent of aggregation is small over a month at these temperatures, but extensive when the solutions are subjected to repeated freeze-thawing from -18 to 25 °C in both D2O and H2O.