The hippocampus produces growth hormone (GH) and contains GH receptors, suggesting a potential role for GH signaling in the regulation of hippocampal function. In agreement with this possibility, previous investigations have found altered hippocampal function and hippocampal-dependent learning and memory after chronic GH administration or deficiency. In this study we applied GH to in vitro rat hippocampal brain slices, to determine if GH has short-term effects on hippocampal function in addition to previously documented chronic effects. We found that GH enhanced both AMPA and NMDA receptor-mediated excitatory postsynaptic potentials (EPSPs) in hippocampal area CA1, but did not alter GABA_A receptor-mediated inhibitory synaptic transmission. GH enhancement of excitatory synaptic transmission was gradual, requiring 60-70 min to reach maximum, and occurred without any change in paired pulse facilitation, suggesting a possible post-synaptic site of action. In CA1 pyramidal neurons, GH enhancement of EPSPs was correlated with significant hyperpolarization and decreased input resistance. GH enhancement of EPSPs required Janus kinase 2 (JAK2), phosphatidylinositol-3 (PI3) kinase, mitogen activated protein (MAP) kinase kinase (MEK), and synthesis of new proteins. Although PI3-kinase and MEK were required for initiation of GH effects on excitatory synaptic transmission, they were not required for maintained enhancement of EPSPs. GH treatment and tetanus-induced LTP were mutually occluding, suggesting a common mechanism or mechanisms in both forms of synaptic enhancement. Our results demonstrate that GH has powerful short-term effects on hippocampal function, and extend the time scale for potential roles of GH in regulating hippocampal function and hippocampal-dependent behaviors.