Using 5-HT7 receptor knockout mice it has been shown that the 5-HT7 receptor is the main mediator of serotonin-induced hypothermia but very little is known about the relevance of 5-HT7 receptors in behaviour. We here report that lack of 5-HT7 receptors leads to a specific learning deficit that is not due to general sensory or behavioural deficits. The knockout mice show impaired contextual fear conditioning but no significant deficits in motor and spatial learning or cued and operant conditioning. In addition, we demonstrate that 5-HT7 receptor knockout mice display decreased long-term synaptic plasticity within the CA1 region of the hippocampus. The results indicate an important role for the 5-HT7 receptor in contextual hippocampal-dependent learning and suggest a possible neuronal correlate for such a role is present within the CA1 region of the hippocampus.