Recent evidence supports a role for neutrophils in the host defense against Mycobacterium avium. To determine whether the depletion of neutrophils has an effect on the outcome of infection in mice as determined by the number of bacteria in liver and spleen, we administered RB6-8C5 anti-neutrophil antibody intraperitoneally both early and late in the infection. Mice were then observed for 14 days and harvested. The number of viable bacteria in liver and spleen was determined. While administration of RB6-8C5 antibody early in infection resulted in a significant increase in the number of bacteria in organs when compared with mice receiving immunoglobulin control, administration of RB6-8C5 antibody late in infection (week 3) did not have an impact on the bacterial load in tissue. Infection of CD18 knockout mice (with impaired neutrophil function), however, did not show a significant enhancement of M. avium growth when compared with that of wild-type control mice. Neutrophils were found to produce increased amounts of TNF-alpha and IL-12 and IL-1 than control uninfected mice during the initial phase of infection, but not after 2 weeks following infection (although IL-1 beta levels continue elevated). The results suggest that neutrophils may have a role in the early (innate) immune response against M. avium but it is only evident after acute depletion of neutrophils and not in mice with chronic neutrophil impairment.