In vitro models were developed to measure cytokine responses to various agents implicated in COPD. These examined the interaction, antagonistic, indifferent, additive or synergistic, between cigarette smoke and infectious agents or their products on cytokine production. Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis and respiratory syncytial virus are common bacterial and viral pathogens isolated from this group of patients. A human monocyte cell line in a model provided a consistent means to examine these interactions, and human peripheral blood monocytes from blood donors were used to study the individual variations in the responses. Effects of virus infection on bactericidal activity of human monocytes common bacterial respiratory pathogens were also examined. An epithelial cell line and monocytes were investigated for the effects due to virus infection on expression of some of the surface antigens relevant to bacterial binding and immune response. The agents used in the study elicited inflammatory responses that could contribute to damage to the respiratory tract and these individual factors could be more harmful in combination. Monocytes from only a proportion of individuals exhibited extreme responses to these agents signifying the role of individual genetic make up in inflammatory processes. Virus-infected monocytes significantly decreased their ability to bind and kill bacteria. Compared with uninfected cells, fewer bacteria bound to virus-infected cells and intracellular bactericidal activity was also decreased. Exposure to a number of harmful factors for longer periods in individuals with certain genetic profiles for inflammation may cause significant damage to the respiratory tract resulting in COPD, and exacerbation in its course.