This study was performed to evaluate the role of products of the 5-lipoxygenase pathway in histamine release from human basophils. AA-861, a specific inhibitor of 5-lipoxygenase, did not inhibit anti-IgE-induced histamine release from human basophils with 6 +/- 11% inhibition at 10(-6)M. Neither was there a marked inhibition of histamine release induced by ionophore A23187 and formyl-L-methionyl-L-leucyl-L-phenylalanine with 16 +/- 10 and 11 +/- 6% inhibition respectively at 10(-6)M of AA-861. In contrast, AA-861 enhanced 12-0-tetradecanoyl-phorbol-13-acetate-induced histamine release with 20 +/- 3% at 10(-6)M. These results suggest that 5-lipoxygenase activation may not play a role in basophil histamine release.