Towards understanding how histamine, a vital neurotansmitter, can perform multiple physiological tasks, an analysis of the different proteins that bind histamine is reported here. Their structural comparison reveals conformational rigidity of histamine. Yet, flexibility in the modes of histamine binding has been observed, which appears to suit specific biological roles of the proteins. These results will be helpful in developing specific antihistamines and also in understanding the pharmacological and toxicological profiles of existing antihistamines. (C) 2003 Elsevier Inc. All rights reserved.