The degree of fat agglutination (the so-called “creaming phenomenon”) was measured in sera from 51 critically ill patients, 200 ambulatory patients and 24 healthy volunteers. A 400-μl serum sample was mixed with 10 μl of a fat emulsion (Intralipid), incubated at 37°C, and examined after 2, 6, and 24 h. Almost all samples from critically ill patients exhibited creaming, as did 31% of the samples from ambulatory patients. Serum samples from healthy volunteers were incubated with purified C-reactive protein (CRP). At a CRP concentration of 40 mg/L, creaming was always observed. Creaming also occurred at normal serum levels of CRP, but at increased concentrations of other serum proteins. Finally, the creaming test was performed with 12 different fat emulsions, mixed with sera from critically ill and healthy subjects. Healthy sera produced no creaming and sera from critically ill patients invariably showed creaming with every emulsion.