Endogenous 5-HT has been proposed as the mediator responsible for cotton dust aqueous extract (CDE)-induced contraction of the isolated rat stomach fundus. It has been previously reported that there is a residual response to CDE in the presence of concentrations of methysergide which completely block the responses to 5-HT. This study confirms the finding and shows that a combination of the cyclooxygenase inhibitor, indomethacin, and the non-selective leukotriene antagonist, FPL55712, (at concentrations which individually do not affect 5-HT or CDE-induced contractility) in combination, significantly blocked CDE-induced contractions (38%) but not those to 5-HT. Whilst the latter results cannot be readily explained, they clearly show that part of the response is not due to 5-HT or 5-HT release mechanisms.