BACKGROUND Potentiation of inhibitory transmissions in the spinal cord is considered to be an important mechanism for the mediation of the immobilizing effects of anesthetics. However, the depressant effects on motoneurons could be counterbalanced by presynaptic effects that inhibit the depressant pathways. Here we investigated the effect of sevoflurane on a disynaptic inhibitory pathway onto motoneurons in a human reflex model. METHODS The study was performed with 9 volunteers receiving sevoflurane anesthesia (end tidal: 0.8% sevoflurane). Reciprocal inhibition was estimated from the depression of the H-reflex following a conditioning stimulation of the muscle spindle afferents from the tibialis anterior muscle. Measurements were performed before, during and after drug administration. RESULTS The inhibition (mean ± SE) amounted to 15.4% ± 6.8%, 1.9% ± 4.2% and 15.7% ± 8.8% for measurements before, during and after sevoflurane administration, respectively. Differences between the anesthetic state and the two controls were statistically significant (mixed-effect ANOVA, p<0.01). CONCLUSIONS Sevoflurane reduces reciprocal Ia-inhibition on motoneurons in humans. These findings seem to contradict the accepted view that sevoflurane enhances inhibitory synaptic transmission. This contradiction might be explained by the inhibitory actions of sevoflurane within the disynaptic pathway prior to the final glycinergic transmission onto the motoneuron. Our results suggest that even in presumably simple pathways, postsynaptic effects of anesthetics could be superimposed by their presynaptic effects.