To determine the role of the histamine H3-receptor on basophils, different specific H3-antagonists were investigated. Incubation of washed leukocytes with N alpha-acylated histamine-derivatives (N alpha-ahd) induced elevated histamine levels. This process turned out to be dependent on dose, time and temperature, but independent of Ca2+ and Mg2+ ions. IgE-mediated histamine release was not modulated. [3H]-L-histidine was not decarboxylated into [3H]-histamine in spite of the observed histamine increase. Highly purified basophils did not show any histamine elevation but purified neutrophils and eosinophils were found to have increased histamine levels even after disintegration and subsequent incubation with N alpha-ahd. It seems that the increased histamine levels result from the cleavage of the applied histamine amides. Other potent H3-antagonists (e.g. thioperamide) neither produced increased histamine levels nor influenced IgE-mediated release from basophil leukocytes. The existence of H3-receptors on human basophils therefore seems unlikely.