CA1 is the major output area for the hippocampus, and current evidence shows that it is excited primarily from ipsilateral and contralateral CA3 pyramidal cells in the rat. Direct connections from the midline thalamic nuclei to the hippocampus have been described anatomically, but the physiological role of these connections has not been reported until the recent observation that these inputs may have a mild excitatory effect (subthreshold for population spikes). In this study, we report a more powerful excitatory effect of thalamic stimulation on the response of the CA1 neurons in the urethane-anesthetized rat. Electrical stimulation to the midline thalamus induced responses similar to responses from stimulation of the contralateral hippocampus (CA3), with well-developed field excitatory postsynaptic potentials and large population spikes. The latency of the CA1 response suggested that the thalamic connection was monosynaptic, and there was a laminar CA1 response profile that depended on the site of stimulation (contralateral CA3 or thalamus). In an initial examination of possible differences in the physiological effects of these two pathways on the CA1 region, we tested both sites for long-term potentiation of CA1, for the effects of repetitive stimulation on CA1 responses (e.g., possible augmenting responses) and for the effect of paired-pulse stimulation. In these three measures, there were clear and statistically significant differences between the effects of CA3 and thalamic stimulation on CA1 responses. This study demonstrates that the well-described thalamic connection to the hippocampus allows for the direct and powerful excitation of the CA1 region. This thalamohippocampal connection bypasses the trisynaptic/commissural pathway that has been thought to be the exclusive excitatory drive to CA1. In addition, preliminary data indicate that the thalamus and CA3 inputs have different physiological effects on CA1 pyramidal cells.