Pseudohyperphosphatemia was noted in four patients with hyperglobulinemia when inorganic phosphate levels were measured on the Vickers M-300 discrete automated analyzer (Vickers, Raritan, NJ) used by our clinical laboratory. When the same samples were reanalyzed after protein removal by sulfosalicylic acid precipitation, ultrafiltration, or more extensive dilution, the measured serum inorganic phosphate levels were invariably normal. The addition of human globulin (but not albumin), to pooled normal sera, caused an increase in serum inorganic phosphate levels as measured by the discrete analyzer. The increase correlated with the amount of globulin added (r = 0.72, P less than 0.05), but measured levels did not reach those observed in the hyperphosphatemic, hyperglobulinemic patients. Identification of 13 additional hyperglobulinemia patients revealed that hyperglobulinemia was not invariably associated with hyperphosphatemia. These data suggest that (1) with discrete automated analyzer use, hyperglobulinemia but not hyperalbuminemia may falsely elevate serum inorganic phosphate levels; (2) increased measured serum inorganic phosphate levels appear to be determined by both the concentration and the physicochemical characteristics of the globulin; (3) physicians should avoid prescribing phosphate binders to hyperglobulinemia patients with "hyperphosphatemia" unless they have ascertained that the serum inorganic phosphate level has been measured in a specimen that is free of protein; and (4) the occurrence of "pseudohyperphosphatemia" should suggest the need for an evaluation to rule out the presence of a monoclonal gammopathy.