A population of prairie decrmice (Peromyscus maniculatus bairdii) maintained in captivity for I7 years (20-25 generations) was compared with the laboratory-reared offspring of a field-caught population in regard to their response to the forced occupation of a novel environment (activity wheels). It was hypothesized that the incidence of self-induced food deprivation had been significantly reduced in the semi-domestic population as a result or genetic changes accompanying the domestication process. Controls were established for handling, social isolation, post-natal maternal environment (fostering) and post-weaning rearing environment (field enclosure vs. laboratory cages). Unrestricted food consumption of the wild genotype subjects was significantly reduced during the first 48 hours in the novel environment while the food consumption of the semi-domestic subjects did not change. This strain differential response to a novel environment could not be explained by strain differences in responses to handling and social isolation nor was it affected by fostering and post-weaning rearing experience. Changes in body weight and activity could not account for the self-induced food deprivation exhibited by the wild-genotype mice. It was concluded that the differential reactivity of the wild and semi-domestic strains may be due to changes in the gene pool of the semi-domestic population resulting from a shift in selection pressures accompanying the transition from field to laboratory environments.