Disappearance rate of injected D<sub>2</sub> from the arterial blood as well as the effect of histamine on the rate were studied in rabbits. The concentrations of D<sub>2</sub> in the serial arterial samples obtained through a Polyethylene tubing inserted into the carotid artery were assayed by the freezing point elevation method of Reaser. At zero time 3 ml of isotonic D<sub>2</sub> in normal saline was injected into the jugular vein and at the same time serial sampling of arterial blood started. The serial sampling interval was either 7.7 sec or 12.3 sec. In the histamine treated animals histamine diphosphate (0,5 mg of histamine base) was injected intravenously 30 minutes prior to the zero time. The following results were obtained. 1. D<sub>2</sub> concentration in arterial plasma water, x, was empirically obtained by the sum of 2 exponential terms of time, x=Ae<sup>kit</sup>+Be<sup>kit</sup>, and its theoretical basis was sought. The first term of the right member of the equation was regarded to be attributable to the compartment P which possessed instantaneous exchange of water with plasma. The second term was postulated to represent the poorly exchangeable compartment. 2. The constant A of the equation was evaluated as 4,37% and 14.3% in the control and histamine treated groups, respectively. B was 1.19% in the control and 0.849% in histamine treated animals. 3. The disappearance rates determined were; k<sub>1</sub>=0.0519±0.0221 sec<sup>-1</sup> k<sub>2</sub>=0.00454±0.00247 sec<sup>-1</sup> in the control group. k<sub>1</sub>=0.1137±0.0290 sec<sup>-1</sup> k<sub>2</sub>=0.00499±0.00204 sec<sup>-1</sup> in the histamine group. 4. In the histamine treated animals the disappearance rate of the first term was larger than that of the control animals, suggesting an enlarged size of the rapidly exchangeable compartment with regard to the plasma water. On the other hand the constant B was decreased by histamine administration, suggesting a distribution of D<sub>2</sub> in an enlarged volume. This view was also made clear by comparing the apparent asymptotes to which the concentration curves of D<sub>2</sub> approached in respective groups. The asymptotes in the histamine treated group showed lower values.
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