We have sampled small mammals on the Konza Prairie Biological Station, in eastern Kansas, from autumn 1981 through the present. One part of this effort has involved sampling rodents and shrews on 14 permanent traplines (20 stations, 15-m interstation intervals and 4 consecutive nights) situated in native tallgrass prairie during each of 29 autumns and 29 springs as well as 6 summers. In these permanent sites, house mice (Mus musculus) were extremely uncommon as illustrated by average abundances of 0.023 mice/100 trap nights (TN) in autumn, 0.022 mice/100 TN in summer and 0.000 mice/100 TN in spring. Precipitation in summer influenced autumn use of tallgrass prairie by house mice; captures only occurred in autumn when precipitation was ≥300 mm in the previous summer. House mice were slightly more likely (though not significantly) to be captured in lowland than upland or hill slope prairie. The distribution of occurrence was not influenced by fire (burned or unburned) or grazing history (grazed or ungrazed). Over our total trapping efforts on Konza Prairie (sampling on the permanent traplines plus other traplines and grids), we captured only 36 house mice or about 0.01 individual/100 TN. Overall, more males (64%) than females were captured; males, on average, were larger (14.0 g) than females (10.5 g) in body size; females typically were non-reproductive (only one of 13 was pregnant) and individuals typically were trapped only once. Captures were distributed broadly in both space and time and lacked predictability (i.e., exhibited an “anti-nested” distribution of captures). These and other patterns suggest that most house mice were transients in the tallgrass prairie. Distribution and abundance of house mice also imply that this introduced species is extremely uncommon and likely will never be invasive in native tallgrass prairie.