The cluster structures observed by means of mass spectrometry for binary mixtures-tert-butyl alcohol (TBA)H2O and tetrahydrofuran (THF)-D2O-with varying mixing ratios exhibit striking contrast, even though both TBA and THF are miscible with water at any mixing ratio. In the TBA-H2O mixtures at TBA mole fractions of (X-TBA) less than or equal to 0.01-0.025, some of the H2O molecules in the H2O clusters are replaced by TBA molecules. For 0.01-0.025 less than or equal to X-TBA less than or equal to 0.2-0.3, the self-aggregation of TBA forms dominant cluster structures, and the hydrogen-bonded water clusters are disintegrated with increasing XTBA. This TBA self-aggregation is reduced with further increasing TBA at X-TBA greater than or equal to 0.3. However, in the THF-D2O mixtures, THF molecules have a weak additional interaction with D2O clusters, and the self-aggregation of THF is not promoted in the THF-D2O mixtures. The D2O clusters still exist, even at a THF mole fraction of X-THF = 0.3. On the basis of the observed cluster structure, the mechanism for the mixing between water and the organic solvent and the controlling factors in the self-aggregation are proposed.