An attempt to explain the significant isotope effect of deuterium and heavy oxygen observed in the MD process was undertaken. A study of the transport mechanism through porous PTFE membranes showed that membrane mass transfer coefficients can be well estimated from the molecular diffusion model or from the combination of Knudsen and molecular diffusion models. The existence of a diffusion isotope effect in membrane distillation enhances the separation factors for (H2O)-O-./HDO and (H2O)-O-16/(H2O)-O-18 enrichment. The discussion of the nature of the isotope effect in MD is presented.