The effect of calcium antagonists on basophil activation was investigated in 14 subjects. Verapamil, methoxyverapamil and diltiazem, in a concentration range of 1-100 microM, exert a concentration-dependent inhibition on the human basophil histamine release induced by calcium ionophore A23187, zymosan activated human serum and grass pollen allergens. This inhibitory effect is highly variable from subject to subject and from drug to drug. At concentrations higher than 200 microM, verapamil, methoxyverapamil and diltiazem induce a calcium independent histamine secretion from basophil leukocytes. This mediator release is associated with an increase in LDH levels in the cell supernatant and seems to be due to a cytotoxic effect.