Chronic psychosocial stress markedly reduces the expression of high‐frequency stimulation (HFS)‐evoked early long‐term potentiation (LTP) in the CA1 region of the hippocampus of anesthetized rats. Immunoblotting was performed to determine changes in molecular levels of key signaling proteins that might be responsible for this inhibitory effect. Western blot analysis of the CA1 region demonstrates that chronic psychosocial stress decreases basal levels of calcium calmodulin kinase II (CaMKII), phosphorylated (P)‐CaMKII, calmodulin, and protein kinase C (PKCγ) while markedly increasing protein phosphatase 2B (calcineurin) levels. The decrease of basal levels of P‐CaMKII may be triggered primarily by excessive dephosphorylation resulting from enhanced basal levels of calcineurin. The decline in the basal levels of the upstream molecules, PKCγ and calmodulin may be a consequence of the diminished basal P‐CaMKII levels. Analysis of signaling molecules in CA1 region of chronically stressed rat subjected to HFS in vivo showed only one difference compared to similarly stimulated control rats; no increase in P‐CaMKII levels. Our results suggest that decreased P‐CaMKII levels may be primarily responsible for the stress‐induced reduction in LTP expression. © 2004 Wiley‐Liss, Inc.