The partition of zinc in human serum between two major zinc-binding proteins, albumin and alpha2-macroglobulin, was studied in 28 control subjects and in 156 hospitalized patients. Albumin-bound zinc was both the major and the more dynamic of the serum zinc components. Over a wide range of values the concentrations of albumin-bound zinc and total serum zinc were highly correlated (r=0.91) with each other, as were concentrations of albumin and albumin-bound zinc (r=0.69). alpha2-Macroglobulin-bound zinc was not strongly correlated either with total serum zinc or with the serum concentration of alpha2-macroglobulin. Twenty-four hour urinary excretion of zinc was not correlated with any of the serum zinc parameters. To a large extent it appears that total serum zinc concentration reflects serum albumin concentration.