Cotton rats are prolific and produce several litters of two to 10 young, averaging about five, a year. The gestation period is approximately 27 days. Females frequently breed again immediately after partus. They develop rapidly. The eyes open in about 36 hours, the incisors erupt on the fifth or sixth day, and the young rats are usually weaned when 15 or 20 days old.
Cotton rats are subject to violent fluctuations in numbers.
Normally, cotton rats occur in moderate to low populations in all parts of the state where ground cover is present. The size of the population is correlated with the amount of suitable habitat, and suitable habitat in turn is correlated with the amount of rainfall. Thus, in the marginal parts of its range this rat is attuned to climatic changes and the population is subject to violent fluctuations. In fact, peak populations are recorded about every 10 years in central Texas. Records reveal a severe outbreak in 1919.