Previous studies showed that responses to TMS of the primary motor cortex (M1) are different during lengthening compared with shortening muscle contractions performed with the contralateral limb. There is also strong evidence to suggest that the ipsilateral M1 is activated during a unilateral task. PURPOSE: To determine if ipsilateral M1 responses to TMS vary according to the type of muscle contraction. METHODS: In Experiment 1, healthy volunteers (n = 12, mean age 22) performed lengthening and shortening isokinetic contractions at 20 deg/s with the left wrist flexors at the same absolute force (20, 40, 60, 80, and 100% of concentric maximal voluntary force, MVC). During the contractions, single-pulse TMS was delivered to the left (ipsilateral) M1 at 120% of resting motor threshold. In Experiment 2, volunteers (n = 10, mean age 24) performed shortening and lengthening contraction at 90% MVC and received paired-pulse TMS in the ipsilateral M1 to evoke intracortical inhibition (ICI, 2 ms) and facilitation (ICF, 10 ms). In both experiments motor evoked potentials (MEPs) were recorded from the resting right flexor carpi radialis (FCR) using surface electrodes. RESULTS: Although the peak-to-peak amplitude of the ipsilateral MEPs was similar (p = 0.132) during shortening (215% SE ± 17.4) and lengthening (238% ± 18), there was a significant contraction type (shortening, lengthening) by contraction intensity (20, 40, 60, 80,100%) interaction (P = 0.025), indicating that M1 output increased more (P < 0.05) with contraction intensity during lengthening than shortening at 80 and 100% MVC. In addition, the contraction type by stimulation condition (Test, ICI, ICF) interaction (F = 6.4, P = 0.008) suggested that ICI diminished more during lengthening (92% ± 11.2) than shortening (69% ±7.2) and rest (53% ± 7.3) and ICF diminished during shortening (116% ±11.2) but increased during lengthening (158% ± 15.4) compared with rest (135% ± 7.3) (all P < 0.05). CONCLUSION: These data are consistent with the hypothesis that ipsilateral responses to TMS vary according to the type of muscle contraction. This specificity is characterized by a generally higher ipsilateral M1 output during lengthening than shortening, including a shift to diminished inhibition and heightened facilitation. Supported in part by NIH R01AG024161