It has been demonstrated in man that the H-reflex is more depressed by presynaptic inhibition than the stretch reflex. Here we investigated this finding further in the alpha-chloralose-anesthetized cat. Soleus monosynaptic reflexes were evoked by electrical stimulation of the tibial nerve or by stretch of the triceps surae muscle. Conditioning stimulation of the posterior biceps and semitendinosus nerve (PBSt) produced a significantly stronger depression of the electrically than the mechanically evoked reflexes. The depression of the reflexes has been shown to be caused by presynaptic inhibition of triceps surae Ia afferents. We investigated the hypothesis that repetitive activation of peripheral afferents may reduce their sensitivity to presynaptic inhibition. In triceps surae motoneurones, we measured the effect of presynaptic inhibition on excitatory postsynaptic potentials (EPSPs) produced by repetitive activation of the peripheral afferents or by fast and slow muscle stretch. EPSPs evoked by single electrical stimulation of the tibial nerve or by fast muscle stretch were significantly depressed by PBSt stimulation. However, the last EPSP in a series of EPSPs evoked by a train of electrical stimuli (5–6 shocks, 150–200 Hz) was significantly less depressed by the conditioning stimulation than the first EPSP. In addition, the last part of the long-lasting EPSPs evoked by a slow muscle stretch was also less depressed than the first part. A single EPSP evoked by stimulation of the medial gastrocnemius nerve was less depressed when preceded by a train of stimuli applied to the same nerve than when the same train of stimuli was applied to a synergistic nerve. The decreased sensitivity of the test EPSP to presynaptic inhibition was maximal when it was evoked within 20 ms after the train of EPSPs. It was not observed at intervals longer than 30 ms. These findings suggest that afferent activity may decrease the efficiency of presynaptic inhibition. We propose that the described interaction between afferent nerve activity and presynaptic inhibition may partly explain why electrically and mechanically evoked reflexes are differently sensitive to presynaptic inhibition.