The effect of deuterium oxide on the locomotor activity rhythm of the house mouse, Mus musculus, was measured in various environmental conditions.1. In the initial experiments, in which mice were kept in constant low (0.2 foot candle) illumination, D2O concentrations of 5% through 30% (in 5% increments) were administered via the drinking water. Increased concentrations lengthened the period, proportionally, with 30% D2O causing a mean period lengthening of 7.4%.2. Increasing the intensity of illumination in constant conditions can lengthen the period of the mouse locomotor activity rhythm. It was felt that deuterium might be changing the way in which the mice interpreted the light intensity, thus changing the period. Both blind mice, and mice kept in constant darkness were tested at various dosages. The results did not differ significantly from those obtained for mice in constant low illumination, thus showing D2O does not act to alter the period by changing the way in which the mice interpret light intensity.3. Concentrations of D2O from 5% to 30% in 5% increments, were administered to mice in LD 12:12 (8). Doses up through 15% mostly caused phase shifts, at 20% some mice rephased and some were not entrained, while at the higher doses, the rhythms were not entrained to the LD cycle.4. To test if increasing intensity of illumination in an LD cycle could diminish the perturbing influence of deuterium on the period and phase of rhythms, 20% D2O was administered to mice in LD 12:12 (0.2), and LD 12:12 (80). The rhythms of all the mice in the first category were not entrained by the LD cycle, while all the mice in the second category were entrained. These data clearly indicate that the brighter the illumination during the light interval of an LD cycle, the stronger are its entraining capabilities of D2O lengthened rhythms.5. The results are discussed in terms of the bearing they have on clock models, and models for entrainment of rhythms to zeitgeber cycles.