The major focus of this Project has been to examine the potential adverse health effects resulting from prolonged inhalation exposure to brevetoxins. The inhalation toxicities of a complex mixture of brevetoxins and brevetoxin antagonists in K. brevis extract was examined in rats, and the toxicity of pure brevetoxin 3 was examined in both rats and mice. Substantial immune suppression in rats, as indicated by a reduction in antibody response to immunization with sheep red blood cells, was consistently the primary response observed. Suppression of antibody forming responses occurred in the absence of frank toxicity to the spleen, changes in lymphocyte populations, or T cell responses to antigen. This immune suppression is important in light of reports in increased emergency room visits for pneumonia during Red Tide episodes identified by Fleming project and decreases in alveolar macrophage function in sheep inhaling brevetoxins in project by Abraham. This proposal will address the following specific aims: (1) To define exposure concentration-response relationships for brevetoxin-induced effects on humoral immunity in rats and to examine the role of macrophage cathepsin inhibition in mediating these effects; (2) To examine the effects of brevetoxin inhalation on recovery from infection in a rat model of influenza including young adult and aged rats; and (3) To determine the immunotoxic potential of brevetoxin in offspring of dams inhaling brevetoxins. These investigations will broaden examination of the exposure concentration-response relationship for brevetoxin-induced effects on antibody responses to antigen, provide insight into the underlying mechanism(s) for the observed immune suppression, examine potential consequences to brevetoxin-induced immune suppression on responses to viral infection; and determine the potential developmental immunotoxicity resulting from perinatal brevetoxin exposure.