Bidirectional modifications in synaptic efficacy are central components in models of cortical learning and memory. More recently, the regulation of synaptic plasticity according to the history of synaptic activation, termed “metaplasticity,” has become a focus of research on the physiology of memory. Here we explore such interactions between long-term potentiation (LTP) and long-term depression (LTD) in the chronically prepared rat. The effects of successive high- and low-frequency stimulation were examined in sensorimotor cortex in the adult, freely moving rat. High-frequency (300 Hz) stimulation (HFS) applied to the white matter was used to induce LTP, and prolonged, low-frequency (1 Hz) stimulation (LFS) was used to induce either depotentiation or LTD. Combined stimulation (HFS/LFS or LFS/HFS) during the induction phase attenuated potentiation effects only if the LFS followed the HFS. LTD induced by LFS alone was expressed as a reduction in the amplitude of both short- and long-latency field potential components, whereas depotentiation was primarily expressed as a decrease in the amplitude of the potentiated long-latency component. In other experiments, LTP (or LTD) was induced to asymptotic levels before applying LFS (or HFS). LFS caused depotentiation of the late component but had no measurable effect on the early component. HFS reversed previously induced LTD, but the potentiation decayed more rapidly than usual. LTP and LTD therefore modulate each other in the awake, behaving rat.