Quinoprotein alcohol dehydrogenases can be inactivated by cyclopropanol, cyclopropanone hydrate, and, depending on whether they can oxidize secondary alcohols, also by cyclopropanone ethyl hemiketal. Only enzyme molecules containing the oxidized coenzyme (PQQ), but not those with the coenzyme in the semiquinone form (PQQH), become inactivated with these compounds. The inactivation process proceeds without proton production or electron acceptor consumption and free radical is not observed in the inactivated enzyme. It could be demonstrated that a stoichiometric relationship exists between enzyme inactivation, PQQ converted, PQQ adduct formed, and cyclopropanol added. Thus the dimeric and monomeric enzyme become fully inactivated with two and one molecule of cyclopropanol, respectively, indicating that the dimeric enzyme contains two independently acting catalytic sites. Inactivation of the enzyme by cyclopropanol and cyclopropanone hydrate produces chromatographically different PQQ adducts. Since cyclopropanemethanol, cyclobutanol and cyclohexanol are not suicide substrates, the inactivation presumably proceeds via a ring opening such as proposed for the metal-ion-catalysed degradation of cyclopropane derivatives. The results are in accordance with our view on the reaction mechanism of these enzymes but not with that of others [Mincey et al. (1981) Biochemistry 20, 7502-7509]. The reasons why their model has to be refuted are discussed.