The suitability of two lipoxygenase inhibitors to study the putative effects of leukotrienes (LTs) in rat isolated perfused mesentery has been assessed. Both the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA) and the dual lipoxygenase and cyclo-oxygenase inhibitor BW 755C depressed vasoconstrictor responses to NA, an effect characteristic of cyclo-oxygenase inhibitors on this tissue. However, depression of responses to NA by NDGA was non-selective since it depressed responses to calcium over the same concentration range. BW 755C possessed some selectivity for inhibition of responses to NA compared to calcium. The difference in relative selectivities between the two inhibitors was confirmed using prostaglandin E2 (PGE2), which reversed responses to NA depressed by BW 755C to a greater extent than those depressed by NDGA. LTC4 and LTD4 neither caused vasoconstriction nor reversed responses to NA depressed by BW 755C. Since NDGA in particular caused depression in this tissue, results using this drug to investigate the possible role of LTs in other blood vessels should be treated with caution.