Wild-trapped and laboratory-reared Peromyscus maniculatus (Wagner) were raised as confined colonies indoors with various stocking densities ranging from 0.026 to 0.100 mice per sq. ft. in pens of 40, 77, and 154 sq. ft. The animals were individually tagged and all pens were censused at weekly or semi-monthly intervals to record animals present, body weights, food consumption, and overt reproductive condition. At the termination of each experiment, all mice were necropsied and organ weights of gonads and adrenals recorded. Histological sections were made of the testes and ovaries. Half the colonies were subjected to density-independent exploitation by removal of 50% of the mice in each litter before weaning. Colonies stocked with the wild-trapped P. m. rufinus failed to establish a regular pattern of successful breeding and were terminated after one year. The succeeding colonies were stocked with the lab-reared P. m. sonoriensis and these did breed regularly, and the young survived to maturity. Reduction of the population growth rate to zero at the equilibrium density was accomplished by a cessation of breeding by the original females after an average of 2.9 litters was produced by each female. This, combined with a failure of the progeny born into the colony ever to produce young, caused the population growth rate to remain at zero for up to the maximum of 52 weeks permitted in this experiment. The exact mechanism appears to be psycho-physiological in nature, in that regression of the germinal tissues of the adults occurs, and these tissues failed to mature in the progeny in all experiments. Reduction of the population growth rate to zero at equilibrium density is not accomplished by mortality of either young or adults, except when wild-trapped mice are used. Density-independent exploitation of the colonies increased the number of litters born, the litter size, and the total number of young born. There was a tendency for higher pre-weaning mortality. The net effect of these changes was a tendency for reduction in the equilibrium density of the exploited colonies, which may indicate that this species under these conditions is not totally self-regulatory; i.e., equilibrium density may be determined by both intrinsic and extrinsic factors. There was no discernible effect of exploitation on the measures of body weight, food consumption, adrenal weight, or adrenal weight per gram of body weight. Many parameters were found to be negatively correlated with stocking density: the length of the reproductive period, numbers of litters born in a colony, total number of young born in a colony, litter size, number of nest boxes occupied by the mice at equilibrium, and the number of mice present in a colony at equilibrium. Some physiological measures proved to be positively correlated with density: progeny weight at three months, adrenal weight, and adrenal weight per gram of body weight.