The effect of long-term exposure to cigarette smoke on the height and specificity of the secondary humoral immune response to influenza was investigated in a murine model system. It was shown that if mice were pre-immunized with a sub-lethal infection of influenza virus and then exposed to cigarette smoke daily for 36 weeks, they were able to mount a secondary immune response of normal height on subsequent challenge with the homologous virus strain. The response, however, was less specific than that elicited in control mice, with high titres of cross-reacting antibody by haemagglutination-inhibition to the following strain in the same antigenic series. Recall of antibody to the previous strain in the antigenic series was not observed in either control or smoke-exposed animals. These results serve to correct an earlier discrepancy between the murine system and human studies in which the response to influenza infection in mice was depressed by prolonged exposure to cigarette smoke, whereas in man the response of smokers did not differ significantly from that of non-smokers. This apparent discrepancy had been caused by a lack of previous experience of influenza in the mice, which had therefore mounted a primary response, compared with the secondary response observed in the human studies.