Streptococcus suis (S. suis) colonizes the tonsils of most healthy pigs. However, in some pigs the bacteria invade causing a septicemia resulting in meningitis, arthritis, serositis, and/or pneumonia. The interaction between S. suis and neutrophils has been reported to be important, but factors involved in the S. suis/neutrophil interaction are unknown. In addition, there are no published models of experimentally induced S. suis disease using exposure of pigs to S. suis alone via the natural route of infection (oral/nasal). A model of this nature is important for the evaluation of virulence factors, vaccines, and treatment regimens. Two studies are presented in this dissertation;The first study was designed to develop a reproducible intranasal S. suis challenge model and to use the model to better understand S. suis-induced disease. Pigs were exposed to S. suis serotype 2, isolate ISU VDL #40634/94, by aerosolization or by intranasal inoculation. The exposure to S. suis was with or without preexposure to a nasal mucosal irritant, ammonia. The results of these experiments indicated that the ammonia pretreatment did not change the pathogenesis of the disease or disease incidence when compared to S. suis alone. Intranasal inoculation resulted in a higher number of animals developing S. suis-induced disease compared to aerosolized S. suis. The outcome following intranasal inoculation of S. suis did not change after the S. suis serotype 2 isolate was passaged in vitro 20 times. Streptococcus porcinus avirulent live vaccine was evaluated for efficacy against S. suis-induced disease using this model. The S. porcinus vaccine reduced S. suis-induced disease incidence, but not significantly (p > 0.05), and was not pursued further;The second study was designed to characterize S. suis factors secreted by S. suis serotype 2 during incubation in saline for two hours. A porcine neutrophil suppressive factor that passed through a 1000 dalton filter was identified. Reverse phase high performance liquid chromatography was used to purify the factor. The suppressive fraction contained guanine and at least two other unknown components that may be other bases and/or nucleosides. The factor suppresses neutrophil iodination, but does not inhibit neutrophil ingestion of Staphylococcus aureus, cytochrome C reduction, or random migration.