THE process of learning involves stable changes in synaptic efficacy for which long-term potentiation (LTP)¹ provides a widely adopted mammalian model. Synaptic modification induced by learning or LTP may involve the action of cell adhesion molecules^2–4. One such candidate is the ubiquitous neuronal glycoprotein Thy-1 (refs 5, 6). In mice in which the gene encoding Thy-1 has been inactivated, we find a regionally selective impairment of LTP in vivo in the hippocampal formation: LTP is normal in area CA1 but strongly inhibited in the dentate gyrus. Spatial learning by Thy-1-deficient mice, as assessed in the watermaze⁷, is unimpaired. Thus LTP in the cortical input to the dentate gyrus seems not to be required for spatial learning.