The local release of histamine is considered to be largely responsible for the early asthmatic response to inhaled allergen, although its contribution to the late response is less well-established. To investigate this we have measured the changes in forced expiratory volume in one second (FEV1), plasma histamine and urinary N tau-methylhistamine, in 10 asthmatics following inhaled allergen. To estimate the significance of any changes, we also measured plasma histamine concentrations following inhalation of histamine by nine normal subjects. Following allergen inhalation, the FEV1 fell a mean maximum 38% (SD 13%) from baseline at 15 min, associated with an increase in plasma histamine from a mean (SD) 0.22 (0.08) to 0.64 (0.47) ng.ml-1 at 10 min. During the late asthmatic response, plasma histamine concentrations did not depart significantly from baseline concentrations. There were no significant changes in urinary N tau-methylhistamine excretion. Inhalation of histamine by normal subjects at concentrations up to 4 mg.ml-1 showed no significant change in plasma concentrations, but at 16 mg.ml-1 there was an increase from a mean (SD) baseline 0.25 (0.10) ng.ml-1 to a mean maximum 0.83 (0.53) ng.ml-1 at 1 min. The early asthmatic response to inhaled allergen in asthmatics is accompanied by a significant increase in plasma histamine, approximately equivalent to an inhaled concentration of 16 mg.ml-1, whereas no significant changes in histamine were found during the late asthmatic response.