Histamine as an important mediator of the allergic reaction has been measured by a number of methods both in whole blood and cell supernatants after in vitro release. We compared the fluorometric histamine assay with two radioimmunoassays and studied detection limit, recovery, cross-reactivity and accuracy in buffer-based standards as well as the sensitivity after IgE-mediated in vitro release from washed cells and whole blood. Our data indicate that the double-antibody RIA (Pharmacia) can be used for studies of basophil histamine release in both whole blood and cell supernatants. Due to significant cross-reactivity to N-methyl-histamine it cannot be used for histamine determinations in plasma. The second radioimmunoassay using succinyl-glycine as an acylating reagent and monoclonal antibodies, which have been raised to acylated histamine, is the most sensitive assay without any cross-reactivity with methylhistamine.