In Australia, outbreaks of house mice (Mus domesticus) cause significant damage to agricultural crops. Rodenticides are used to reduce damage to crops, but the demographic consequences of applying rodenticides are poorly understood. Furthermore, it is not known whether the reduction induced by rodenticides would be similar to that of a natural crash in abundance at the end of mouse outbreaks. I compared the demographic responses of populations of mice to broad-scale field application of fast-acting, acute rodenticides (strychnine and zinc phosphide) in three grain-growing regions of Australia on baited and unbaited sites through live-trapping of mouse populations before baiting and up to four months after baiting. The reductions in population density in each region immediately after baiting were <40%, 92% and 98%. There were few consistent changes in demographic responses across the three regions for bodyweight (no change, increased or decreased), proportion of juveniles (increased or decreased), sex ratio (no change or bias towards females), survival (no change or decreased) and relative body condition (no change or increased). The differences in demographic responses appeared to be related to differences in the efficacy of the rodenticide. A natural crash in densities occurred over a 2–4-week period after baiting and induced a >85% decline in population densities across all regions on baited and unbaited sites. The natural crash caused increases and decreases in bodyweights, a reduction in the proportion of juveniles, male bias, poor survival and poor relative body condition. Poor survival was the only demographic parameter that was consistent for baiting and the natural crash. Five of seven demographic responses for mice during the natural crash were similar to those found in the literature for the decline phase of cyclic vole and lemming populations in the Northern Hemisphere. These results raise the question of whether mouse populations should be baited if a natural crash would occur anyway, but the timing of the natural crash is always uncertain and rodenticides are inexpensive.