Participation of histamine in the inflammatory reaction produced by carrageenan was studied. Mepyramine did not influence the course of the inflammatory reaction. In contrast to when mepyramine was used, there was a significant inhibition of carrageenan oedema when cimetidine was used. Pretreatment of animals with compound 48/80 significantly reduced the oedema formation. Neither mepyramine nor cimetidine reversed the inhibition of rat paw swelling produced by histamine liberators. It is concluded that histamine participates in carrageenan oedema via its H2-receptors and that the anti-inflammatory effect of compound 48/80 is not connected with the 'anti-inflammatory' action of liberated histamine.