The olfactory and the trigeminal systems have a close relationship. Most odorants also stimulate the trigeminal nerve. Further, subjects with no sense of smell exhibit a decreased trigeminal sensitivity with unclear underlying mechanisms. Previous studies indicated that single stages of trigeminal processing may differently be affected by olfactory loss. A better knowledge of adaptive and compensatory changes in the trigeminal system of subjects with acquired anosmia (AA) will improve the understanding of interactive processes between the 2 sensory systems. Thus, we aimed to assess trigeminal function on different levels of processing in subjects with AA. Subjects with AA showed larger electrophysiological responses to irritants obtained from the mucosa than healthy controls. On central levels, however, they exhibited smaller event-related potentials and psychophysical measures to irritants. Over 9 months, they exhibited an increase in trigeminal sensitivity. Subjects with recovering olfactory function showed an even more increased peripheral responsiveness to irritants. These data suggest dynamic mechanisms of mixed sensory adaptation/compensation in the interaction between the olfactory and trigeminal systems, where trigeminal activation is increased on mucosal levels in subjects with AA and amplified on central levels in subjects with a functioning olfactory system.