A method is described for concurrent investigation of long-term potentiation (LTP) in the left and right CA1 synapses in dorsal hippocampi in guinea pig in vivo. Briefly, animals are anesthetized with urethane, and small access holes are made in the skull through which electrodes are lowered to stimulate the left CA3 and record from both CA1 regions. Using this animal model, we have found that LTP is produced in both CA1 regions, following conditioning stimulation to the left CA3. However, in some animals LTP occurred in the left CA1 without concomitant synaptic potentiation in the contralateral CA1. We also observed that in some experiments synaptic potentiation in the contralateral CA1, when present, decayed to baseline levels even though LTP persisted in the ipsilateral CA1. To conclude, our data on bilateral LTP demonstrates findings that are best addressed in vivo. © 2001 Elsevier Science B.V. All rights reserved.