Intracellular recordings were made from 117 neurons in the motor cortex of anesthetized cats. The pyramidal tract (PT) and VL nucleus of thalamus were stimulated in order to activate the neurons from two directions. 1. PT cells were conditioned by antidromic trains (10--50 cps for 4--15 s) and by paired PT and VL stimuli with different intervals and sequences. The VL-EPSPs were examined before and after conditioning, to find differences in efficacy in giving rise to spikes. The conditioning procedures resulted in a remarkable facilitation of VL-EPSPs, manifesting itself as a significant rise of efficacy in generating spikes, a shortening of peak latency and in some cases, an enhancement of background firing. 2. In non-PT neurons the same conditioning procedures elicited heterosynaptic facilitation and a rise in firing activity. 3. Intracellularly injected square wave pulses also resulted in facilitation of VL-EPSPs. 4. Pairings of PT and VL stimuli were more effective than trains in evoking conditioned changes. 5. Plastic modifications were observed in the 13.7% of the neurons subjected to conditioning procedures. 6. The authors assume that synchronous activity of the pre- and postsynaptic neurons is a highly important condition for plastic changes in the efficacy of synaptic transmission.