Our results indicate that benzodiazepine (Bz) treatment time, greater than 2-3 months, induce a decrease of both specific and nonspecific responses. Mice treated for different times with diazepam or chlordemethyldiazepam showed decreased survival to experimental Salmonella typhimurium infections after three months of treatment. Adherence, expressed as the polymorphonuclear cells (PMN) capacity to attach to nylon wool, was impaired after 7 days of treatment. Longer treatments further increase this impairment. PMN from mice treated with Bz for 90 days also demonstrate on impaired chemotaxis and phagocytosis for Saccharomyces cerevisiae. Monocytes from mice treated for 7 days secreted more IL-1 alpha then controls; the antibody titer in mice given to prolonged treatment progressively diminished compared to controls. Con A or LPS stimulated lymphocytes showed an increase of H3-thymidine incorporation from mice treated for a short time and conversely a decreased incorporation when taken from mice that underwent longer treatments. Benzodiazepines were therefore found to affect PMN chemotaxis and phagocitosis, general immunity and survival of mice to infections.