Nontypeable Haemophilus influenzae are increasingly being recognized as an important cause of disease in the lower respiratory tract. Information about the pathogenesis of these infections has been limited until recently by the paucity of experimental animal models for studying the host-parasite interaction in vivo. Three different animal models for investigation of the interaction of nontypeable H. influenzae with the lower respiratory tract have been used: Two involve the evaluation of short-term pulmonary clearance in mice or rats, while a new, long-term infection model in rats mimics the more chronic bronchopulmonary infections sometimes caused by these organisms. Results obtained in these three model systems indicate that both humoral and cellular immune mechanisms are involved in immunity to lower respiratory tract disease due to nontypeable H. influenzae.