Mutations at the NPR1 genetic locus are known to inactivate (totally or partially) at least five distinct ammonia-sensitive permeases. Mutants with thermosensitive NPR1 gene product (nprts) have been used to discriminate between three possible roles of this protein, namely (a) a common constituent of a set of ammonia-sensitive permeases; (b) a common activator of these permeases; (c) a common positive factor necessary for their synthesis. Inactivation of the general amino-acid permease was observed upon transfer of nprts mutant cells to a non-permissive temperature. Under the same conditions, the general amino-acid permease of the wild-type cells remained active for several hours even when protein synthesis was inhibited by nitrogen starvation or by cycloheximide. Mutations at three unlinked loci, namely the PGR site (located in the GAP1 structural gene of the permease), and the unlinked MUT2 and MUT4 loci restore the general amino-acid permease activity in npr1 mutants. The results are interpreted as indicating that the NPR1 product is necessary for the reactivation of the general amino-acid permease which seems to be continuously inactivated by a regulatory process mediated by the MUT2 and the MUT4 gene products acting at the level of the PGR site of the general amino-acid permease molecule. The proline permease and the ureidosuccinic-acid permease seem to be subject to the same double regulation by inactivation-reactivation of the permeases and by repression of their synthesis. A tentative scheme of the regulation of the general amino-acid permease is presented.