Methacholine dose response curves (DRC) in asthmatic subjects are characterized by a leftward shift and increased maximal response. Allergen inhalation in atopic subjects shifts the DRC to the left, but the effect on the shape is unknown. This study was designed to investigate the effect of allergen inhalation on the maximal response plateau of the methacholine DRC in 16 atopic subjects; nine had mild asthma and seven had rhinitis. They were challenged with allergen and with control solutions in a single-blind design. Methacholine challenges (up to 199 mumol) were performed at baseline and 24 h after the control and allergen challenges. A plateau of the DRC was defined as a difference of less than 5% in FEV1 between the last two or more doses. The maximal response was obtained by averaging the values on the plateau and was reached by all except one subject. Allergen inhalation induced an early asthmatic response (EAR) in all subjects and an additional late asthmatic response (LAR) in 6 subjects. In subjects with an EAR alone the maximal response to methacholine 24 h after allergen challenge was not different from control (mean difference, 2.9% fall in FEV1; p greater than 0.05). In subjects with LAR, the mean value for the maximal response increased from 28.5% after control to 36.5% after allergen (mean difference, 8.0%; p less than 0.05). Of six subjects who developed LAR two lost the plateau on the DRC after allergen challenge. We conclude that allergen inhalation increases the maximal response to methacholine in those subjects who have a LAR.