Activin plays a role in neuronal development and protection. To gain insight into its physiological function in the mature brain, we disrupted activin signaling in a forebrain-specific fashion. For this purpose, we generated transgenic mice expressing a kinase-deficient, dominant-negative mutant of activin receptor IB (dnActRIB) in hippocampal neurons under the control of the CaMKII promoter, thereby excluding an effect of the transgene on pre- and early postnatal development. Hippocampal slices were prepared from wild-type (wt) and two lines of transgenic (tg) mice 2 - 4 months old. Analysis of excitatory synaptic transmission showed that in CA1 pyramidal cells of tg mice, the NMDA component was significantly smaller compared to neurons from wt mice. As a consequence, hippocampi from tg mice displayed significantly less LTP than hippocampi from their wt littermates. At inhibitory synapses, disruption of activin signaling enhanced tonic inhibition through GABA(A) receptors, but strongly diminished the response to diazepam. Our data suggest that activin signaling tunes excitatory and inhibitory transmission in a fashion that is likely to influence both cognitive and affective processes of the adult brain.