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ABSTRACT Increased parental relatedness occurs in small wild populations and in closed colonies in captivity and reduces offspring fitness. A closed colony ofPeromyscus maniculatusis maintained as genetically diverse stock at the Peromyscus Genetic Stock Center since 1963. Breeding records are available for all the years of breeding in captivity, which allows evaluation of the breeding performance since the inception of the stock. Kinship calculations showed that increased parental relatedness results in offspring loss, which is consistent with the operation of inbreeding depression and is common in small populations, both wild and captive. Nonetheless, an adaptive response was recorded that mitigated the adverse consequences of inbreeding and contributed to the long‐term stability of the colony: When parental relatedness increased, more offspring were produced, resulting in the overall number of viable offspring being unaffected. The underlying mechanism involved adjustments in the interval for mating between related parents, causing the production of more litters. These adaptive changes indicate that the harmful consequences of inbreeding may be partially relieved by mechanisms involving changes in the animals' reproductive strategy. The availability of the breeding records ofP. maniculatusenables the performance of additional studies asking different questions regarding the breeding dynamics of a closed colony under regulated conditions.