Mice reproduce interesting effects in auditory discrimination learning and knowledge transfer discussed in human studies: (i) the advantage in the transfer from a hard to an easy task by benefits from transfer of procedural knowledge and information-integration learning, and (ii) the disadvantage in the transfer from easy to hard tasks by inability to generalize across perceptually different classes of stimuli together with initially unsuccessful attempts to transfer cognitive skills from one task to the other. House mice (NMRI strain) were trained in a shuttle-box stimulus discrimination task. They had to discriminate either between two pure tones of different frequencies (PT) or between two different modulation frequencies of an amplitude-modulated tone (AM). Then transfer of knowledge between these two tasks was tested. Mice rapidly learned PT discrimination within two to three training sessions (easy task). AM discrimination learning took longer and did not reach the high performance level of PT discrimination (hard task). No knowledge transfer was detected in animals first trained with the easy (PT) followed by the hard (AM) discrimination task. Mice benefited, however, from knowledge transfer when the AM discrimination was followed by the PT discrimination. When the task changed, confusion of conditioned stimuli occurred if the carrier frequency of the AM was the same as one of the frequencies in the PT task. These results show a hard-to-easy effect when possible knowledge transfer is tested between qualitatively different stimulus classes. The data establish mice as promising animal model for research on genetics of auditory perception and learning.cognitive skill learning | go/no-go paradigm | hard-to-easy effect | shuttlebox | stimulus generalization C omplex forms of auditory learning, such as generalization of stimuli within and across physical categories or transfer of knowledge from one stimulus discrimination task to another, are known from humans (1-6) but rarely have been investigated in other mammals (5,7,8). Research in mammalian models is important, however, for an in-depth understanding of neural mechanisms and the genetics of learning abilities and performances. The mouse (Mus musculus), with its great potential for studying genetic effects on auditory perception, learning, and motor performance, is an ideal candidate species for investigations of auditory learning, because in normal-hearing mice many hearing abilities and functions of processing sounds in the auditory system are already known (9-11). What is missing is an automated and reliable learning paradigm for mice that can be adapted to a variety of learning tasks (e.g., detection, discrimination, generalization, transfer learning), showing that learning rules derived from human studies apply to mice. The shuttle-box seems to be the appropriate learning apparatus because it has been used successfully in simple learning and stimulus detection tasks in mice (12-15) and in complex auditory discrimination and memory tasks in another rode...