Input from primary somatosensory cortex (S1) to primary motor cortex (M1) is important for high-level motor performance, motor skill learning and motor recovery after brain lesion. This study tested the effects of manipulating S1 excitability with paired associative transcranial stimulation (S1-PAS) on M1 excitability. Given the important role of S1 in sensorimotor integration, we hypothesized that changes in S1 excitability would be directly paralleled by changes in M1 excitability. We applied two established protocols (S1-PASLTP and S1-PASLTD) to the left S1 to induce long-term potentiation (LTP)-like or long-term depression (LTD)-like plasticity. S1 excitability was assessed by the early cortical components (N20–P25) of the median nerve somatosensory-evoked potential. M1 excitability was assessed by motor-evoked potential amplitude and short-interval intracortical inhibition. Effects of S1-PASLTP were compared with those of a PASLTP protocol targeting the left M1 (M1-PASLTP). S1-PASLTP and S1-PASLTD did not result in significant modifications of S1 or M1 excitability at the group level due to substantial interindividual variability. The individual S1-PAS-induced changes in S1 and M1 excitability showed no correlation. Furthermore, the individual changes in S1 and M1 excitability induced by S1-PASLTP did not correlate with changes in M1 excitability induced by M1-PASLTP. This demonstrates that the effects of S1-PAS in S1 are variable across individuals and, within a given individual, unrelated to those induced by S1-PAS or M1-PAS in M1. Potentially, this extends the opportunities of therapeutic PAS applications because M1-PAS ‘non-responders’ may well respond to S1-PAS.