Transcranial magnetic stimulation (TMS) of the human motor cortex elicits direct and indirect (I) waves in the corticospinal tract. Facilitatory I wave interaction has been demonstrated with a suprathreshold first stimulus (S1) followed by a subthreshold to threshold second stimulus (S2). Intracortical inhibition (ICI) and intracortical facilitation (ICF) can be studied by another paired TMS paradigm with a subthreshold conditioning stimulus (CS) followed by a suprathreshold test stimulus. Facilitatory I wave interaction in motor representations other than the hand area and its relationship to ICI and ICF has not been studied. We studied I wave interaction, ICI and ICF in an intrinsic hand muscle (abductor pollicis brevis, APB), in a proximal arm muscle (biceps brachii, BB) and in a lower limb muscle (tibialis anterior, TA) in 11 normal subjects. I wave facilitation was studied by paired TMS at 24 interstimulus intervals (ISIs) from 0.5 to 5.1 ms. For APB and TA, facilitation occurred in three distinct peaks at ISIs of 0.9-1.7, 2. 5-3.5, and 4.1-5.1 ms. For BB, facilitation was significant for the first two peaks. The latencies of the peaks were similar among different muscles, but the magnitude of facilitation was much greater for APB and TA compared with BB. For all three muscles, changing the S2 to transcranial electrical stimulation (TES) resulted in much less facilitation of the first peak. For APB, there was significant I wave facilitation with S2 at 72% motor threshold (MT). The same stimulus used as the CS did not elicit ICF at ISI of 15 ms, suggesting that the threshold for eliciting I wave facilitation is lower than that for ICF. For BB and TA, there was no I wave facilitation with S2 at 90% of APB MT, and the same stimulus used as CS led to ICI. Thus in BB and TA the threshold for eliciting ICI is lower than that for I wave facilitation. We conclude that the circuits that mediate I wave interactions are present in the proximal arm and lower limb representations of the motor cortex. I wave facilitation occurs predominately in the cortex and may be primarily related to the monosynaptic corticomotoneuronal (CM) system. The reduced I wave facilitation for BB compared with APB and TA may be related to less extensive CM projection and involvement of other polysynaptic descending pathways. I wave facilitation, ICI, and ICF appears to be mediated by different neuronal circuits.