The transmission across synapses of la afferents on spinal motor neurons was investigated in 30 healthy subjects and 25 spastic multiple sclerosis patients. Slow passive stretch (17°/s) of the soleus muscle evoked a pronounced depression of the soleus Hoffmann reflex (H-reflex) lasting for more than 10 s in the healthy subjects. This depression was less pronounced and had a shorter duration in the spastic patients. A tap applied to the biceps femoris tendon also produced an inhibition of the soleus H-reflex, which was larger in the healthy subjects than in the spastic patients. This inhibition only lasted for 300–400 ms. Finally, stimulation of the femoral nerve (FN) produced a facilitation of the soleus H-reflex, which was larger in the spastic patients than in the healthy subjects. The inhibition of the H-reflex evoked by the biceps femoris tendon tap is known to be caused by presynaptic inhibition of the la afferents, which mediate the reflex. The facilitation of the soleus H-reflex produced by FN stimulation has also been shown to be influenced by changes in presynaptic inhibition. The increased facilitation from the FN and the decreased inhibition from the biceps femoris tendon tap onto the soleus H-reflex in spastic patients are thus both compatible with a deficient presynaptic inhibition in these subjects. The long lasting depression of the reflex evoked by a previous slow stretch of the soleus muscle is most likely caused by a decrease of the probability of transmitter release from the la afferents. The decrease of this depression in spastic patients suggests that mechanisms other than presynaptic inhibition may contribute to changes in the efficiency of transmission across the synapses of la afferents in spastic patients and thus contribute to the exaggeration of stretch reflexes seen in these patients.