Mastitis caused by gram-negative infections is of increasing importance on modern and well-managed dairy farms. Without a doubt, E coli tends to be the most important cause of these gram-negative infections when the data are tallied across farms.1 However, more precise investigation of individual farms often reveals a farm-specific infection pattern where a single gram-negative bacterial species predominates. Several farms with a predominance of “other” gram-negative IMIs may be observed. We have shown the presence of outbreaks on individual dairy farms with K pneumoniae, S marcescens, and Enterobacter cloacae. On farms with a predominance of these “other” gram-negative infections, a detailed epidemiologic investigation may reveal the source of these infections. It is quite surprising to identify the difference in host immune response pattern and the associated clinical and subclinical presentations of IMIs due to the different gram-negative organisms. Experimental and field observations would suggest that among the gram-negative bacterial causes of mastitis, Klebsiella spp are causing the most severe cases, closely followed by E coli and then much less clinical severity is observed in Serratia spp and Enterobacter spp cases. The precise mechanisms that would explain the difference in clinical severity are not known, but the most likely explanation appears to be the structure of the lipid A fraction of the LPS of the bacterial species. Important differences in the lipid A fraction of LPS between and within bacterial species are observed. The prevention of IMIs with gram-negative bacteria has components that are generic across species and components that are species specific. Generic prevention may be obtained by improving hygiene and reducing exposure of teat ends to environmental contamination. Also the use of a J5 bacterin is expected to provide some reduction in severity of gram-negative IMIs across bacterial species. Specific prevention programs will depend on the actual transmission behavior of the dominant species causing IMIs in the herd. Several clonal outbreaks of gram-negative bacterial species have been described. In such situations, optimal milking procedures, segregation and culling of infected animals, and targeted treatment would be advisable. Even more specific are the prevention procedures associated with S marcescens outbreaks, where resistance against specific biocides will lead to transmission of infection through teat disinfectants. Removal of these biocides from the cow environment is than essential. Antimicrobial treatment of gram-negative bacteria has often considered to be of limited value and treatment should be more targeted toward cow survival and reduction of clinical symptoms. More recently, extended treatment with a third-generation cephalosporin was reported to be efficacious in the treatment of E coli and Klebsiella spp but not of E cloacae. Further investigations in effective treatment protocols for gram-negative IMIs are warranted.