We present a novel method, canonical adiabatic free energy sampling (CAFES) that allows for the efficient exploration of the free energy surface of a subsystem (S) embedded in an environment (E) using mol. dynamics simulations. The dynamics of S is decoupled from the environment by introducing fictitious masses that ensure that S evolves slowly and adiabatically on the potential of mean force generated by E. In addn., the decoupling enables the use of different temps. for the two parts of the system without introducing an irreversible heat flow. Using a higher temp. for the subsystem, a high efficiency for the sampling of rare events on the phys. free energy surface is obtained. The performance of this approach is demonstrated with a conformational anal. of a Gly-Ala dipeptide in aq. soln. Rare conformational transitions, which naturally occur on a millisecond time scale, are obsd. within a few nanoseconds of a classical mol. dynamics simulation. The same method has also been applied in a hybrid Car-Parrinello/classical mol. dynamics investigation of the proton-catalyzed conversion of 2-bromoethanol to dibromoethane in water. Using CAFES, the anchimeric assistance of the bromine atom and the occurrence of a bromonium ion intermediate, a process which involves a barrier of ca. 23 kcal/mol, is obsd. spontaneously on the subnanosecond time scale. [on SciFinder (R)]