Feline infectious peritonitis virus (FIPV), an alpha Coronavirus, is the causative agent of a fatal immune mediated disease in cats. It is currently unclear if this virus circulates in the field or develops in felines that are infected with Feline enteric coronavirus. To better understand the genomic changes associated with viral adaptation, we sequenced the complete genomes of FIPV WSU 79-1146 at different tissue passage levels: passage 1, passage 8, and passage 50 tissue culture. Twenty-one amino acid differences were observed in the polyprotein 1a/ab between the different passages. Only one residue change was observed in the spike glycoprotein, which reverted back on subsequent passages, four changes were observed in the 3c protein, and one change was observed in each 3a, small membrane, nucleocapsid and 7a proteins. The mutation rate was calculated to be 5.08-6.3 × 10(-6) nucleotides/site/passage in tissue culture suggesting a relatively stable virus. Our data show that FIPV has a low mutation rate as it is passed in cell culture but has the capacity for change specifically in nsp 2, 3c, and 7b as it is passed in cell culture.