Signs and symptoms of an acute intra-abdominal emergency developed in a 26-year-old man; this emergency prompted surgical exploration. It was discovered that he had a devitalized small bowel as a result of mesenteric vein thrombosis. An extensive evaluation for hypercoagulable states disclosed that he had a normal total protein S concentration, but by assay and on crossed immunoelectrophoresis studies, he had a decreased concentration of free protein S. A family study demonstrated protein S deficiency in his father and in a sister. On a subsequent determination, the propositus had a decreased concentration of total protein S. This case illustrates the association of protein S deficiency with mesenteric thrombosis and serves to caution that a single determination of total protein S is not an adequate evaluation when the index of suspicion for a hypercoagulable state is high.