The binding of ethanol and 1,1,1-trifluoroethanol (TFE) to both the H-mv and H-ox forms of soluble methane monooxygenase (sMMO) in solution has been studied by Q-band (35 GHz) CW and pulsed ENDOR spectroscopy of H-1 H-2 and F-19 nuclei of exogenous ligands. As part of this investigation we introduce F-19, in this case from bound TFE, as a new probe for the binding of small molecules to a metalloenzyme active site. The H-mv form was prepared in solution by chemical reduction of H-ox. For study of H-ox itself, frozen solutions were subjected to gamma-irradiation in the frozen solution state at 77 K, which affords an EPR-visible mixed-valent diiron center, denoted (H-ox)(mv), held in the geometry of the diiron(III) state. The F-19 and H-2 ENDOR spectra of bound TFE together with H-1.2 ENDOR spectra of bound ethanol indicate that the alcohols bind close to the Fe(II) ion of the mixed-valence cluster in Hmv and in a bridging or semi-bridging fashion to H-ox. DMSO does not affect the binding of either of the ethanols or of methanol to H-ox, nor of ethanol or methanol to H-mv. It does, however, displace TFE from the diiron site in H-mv. These results provide the first evidence that crystal structures of sMMO hydroxylase into which product alcohols were introduced by diffusion represent the structures in solution.