Primed burst (PB) potentiation is a long-term increase in CA1 population spike amplitude produced by brief physiologically patterned electrical stimulation of the hippocampal commissure. Exposure of rats to a novel environment resulted in a blockade of short-term (Post-tetanic potentiation, PTP) and long-term (PB potentiation) plasticity in all cases (n = 6). When the animals had extensive exposure to the environment (14 consecutive days), PTP and PB potentiation occurred. With placement of the rats in a second novel environment, once again, neither PTP nor PB potentiation was observed. Placement of rats in each of the two novel environments produced a significant increase in serum corticosterone levels, while placement in the familiar environment produced no increase in response. These findings support the hypothesis that hippocampal plasticity is repeatedly susceptible to modulation by the stress of forced exposure to a novel environment.