We compared the effects of two histamine receptor blocking agents, chlorpheniramine (H1) and cimetidine (H2) on the airways of healthy and asthmatic subjects. Eleven healthy subjects and ten asthmatic patients underwent histamine aerosol challenge. A threshold dose (T) for response to histamine was determined for each subject using maximal expiratory flow rates on partial expiratory flow rates on partial expiratory flow volume curves (MEF40 %[P]). On subsequent study days, the subjects were pre-treated with 8 mg of chlorpheniramine, 300 mg of cimetidine or a lactose placebo. Histamine challenge was performed two hours later with the individual's own T dose and doses one dilution below (T-1) and one dilution above (T+1) that dose. In both asthmatic and healthy subjects chlorpheniramine significantly reduced the bronchoconstrictor responses to histamine (p less than 0.02 and 0.05, respectively) as measured by MEF40 percent (P) at the T dose. When treated with cimetidine asthmatic patients displayed significantly more bronchospasm at T than with placebo (p less than 0.035). By contrast, pretreatment with cimetidine did not alter airway responses to histamine in healthy subjects when compared to placebo. We conclude that H2 receptors mediating bronchodilatation can be demonstrated in asthmatic patients but not in healthy subjects.