An extract of the plant feverfew (Tanacetum parthenium) produces a dose-dependent inhibition of histamine release from rat peritoneal mast cells stimulated with anti-IgE or the calcium ionophore A23187. Greater inhibition of anti-IgE-induced histamine release was achieved with feverfew compared with the inhibition of A23187-induced release. Inhibition of anti-IgE-induced histamine release by feverfew extract was observed when the drug was added simultaneously with anti-IgE and the inhibitory activity increased only slightly when the drug was preincubated with the cells for 5 min before anti-IgE stimulation. In this respect feverfew differs from cromoglycate and quercetin. Feverfew extract inhibited anti-IgE-induced histamine release to the same extent in the absence and presence of extracellular glucose. It is concluded that feverfew extract contains a novel type of mast cell inhibitor.