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Ceruloplasmin labeled with (67)copper and administered intravenously to dogs, control human subjects, and patients with excessive gastrointestinal loss was shown to fulfill the requirements for a label for quantification of gastrointestinal protein loss. The radiocopper moiety was poorly absorbed from the gastrointestinal tract, not actively secreted into the intestinal tract, and did not alter significantly the metabolism of ceruloplasmin. Approximately 70% of the body pool of ceruloplasmin in both dog and man was within the intravascular space. In control human subjects the mean ceruloplasmin concentration was 30 mg per 100 ml with total circulating and total body ceruloplasmin pools of 15.5 and 22 mg per kg, respectively. In patients with excessive gastrointestinal protein loss secondary to intestinal lymphangiectasia, the serum ceruloplasmin concentration was reduced to 16 mg per 100 ml with a comparable reduction in the total circulating and total body ceruloplasmin pools to 8.8 and 12 mg per kg. The survival half-time of ceruloplasmin was 6.1 days in normal human subjects and 4.5 days in normal dogs. From 1.0 to 1.9% of the intravascular pool of ceruloplasmin was lost into the gastrointestinal tract of the dog per day, representing less than 11% of the over-all metabolism of this protein. In control human subjects from 1.9 to 3.9% of the intravascular pool was lost into the gastrointestinal tract each day, representing a maximum of from 11 to 22% of the over-all metabolism of this molecule. In contrast, patients with intestinal lymphangiectasia had a markedly shortened ceruloplasmin survival of 3.1 days, with from 15 to 40% of the intravascular pool of ceruloplasmin cleared into the gastrointestinal tract daily. This represented 76% of the over-all metabolism of this protein. Thus, although bulk loss of serum proteins into the gastrointestinal tract does not normally appear to be a significant factor in protein metabolism in normal dogs and men, such loss is a major factor in the pathogenesis of the hypoceruloplasminemia noted in patients with intestinal lymphangiectasia.