Normal host defense mechanisms against bacterial pathogens include a variety of inflammatory, hematologic and immunologic processes. An outbreak of mycobacteriosis in a commercial hybrid striped bass culture facility allowed the correlation of disease stage with splenic immunologic parameters, including histopathology, hematopoietic cell counts and macrophage activation. Splenic macrophage metabolic oxidative burst (chemiluminescent response) and the capacity to phagocytize fluorescent microspheres were determined by flow cytometry. Cellularity of the spleen was markedly and approximately equivalently reduced in mycobacterium-infected fish relative to uninfected controls, regardless of infection stage. In contrast, splenic macrophages from infected fish displayed increased chemiluminescent responses at all stages of infection, in an approximate stage dependent manner. The phagocytic capacity of phorbol myristate acetate (PMA)-activated splenic macrophages was different from control only at the most advanced stage of infection, at which time it was significantly reduced relative to control levels.