The present studies tested the ability of 1,8-cineole to produce inflammatory oedema in the hind paw of the rat and verified the possible involvement of mast cells in the response. Subplantar injection of 1,8-cineole (10, 15 and 20 microl/paw) induced a dose-dependent paw oedema which was apparent within 30 min. At higher doses the oedema effect was persistent, peaked at 2 h, and then decreased gradually but was still pronounced at 24 h post injection. In contrast, the oedema produced by mast cell degranulator compound 48/80 (10 microg/paw) had a rapid onset with a peak effect at the first hour, followed by a gradual decrease thereafter and at 24 h post injection it was almost absent. The oedema response to 20 microl 1,8-cineole was significantly inhibited throughout its time-course in rats pretreated with antihistaminic and antiserotonergic drugs such as diphenhydramine, methysergide and cyproheptadine or with ketotifen, a mast cell stabilizer. A more effective blockade of the oedema response was, however, observed in rats depleted of mast cell granules by systemic treatment with compound 48/80. Furthermore, 1,8-cineole was able to cause rat peritoneal mast cell degranulation (94%) in vitro, in a concentration as low as 0.3 microl/ml, which was almost comparable to that produced by 0.1 microg/ml of compound 48/80. The data provide evidence of a key role for the mast cell in 1,8-cineole-induced hind paw oedema in the rat.