Earlier studies have shown that feeding of olive oil to rats substantially increased the plasma protein in the intestinal lymph. The possibility of histamine mediating this response was examined. The plasma protein escape from intestinal circulation after olive oil feeding was measured in rats in terms of the amount of Evans Blue labelled plasma protein found in the intestinal lymph. Animals treated with histamine antagonists (H1-receptor antagonist pyrilamine, 16-22 mg/kg i.p., plus H2-receptor antagonist Burimamide, 12-16 mg/kg i.p.) did not show an increase in the quantity of lymphatic plasma protein. Heparin pretreatment which releases the histaminolytic enzyme, diamine oxidase, into the interstitial space also prevented the increased accumulation of labelled plasma protein in the lymph after olive oil ingestion. Based on these observations, histamine appears to act on the intestinal microcirculation during olive oil absorption and allows larger quantities of plasma proteins to leave the intestinal circulation.