In humans, intramuscular injection of hypertonic saline elicits pain, whereas nerve growth factor (NGF) does not. On the other hand, NGF i.m. induces a long-lasting hyperalgesia. Here, the neuronal basis of these effects was studied at the spinal level. In anaesthetised rats, lumbar dorsal horn neurones were recorded intracellularly before, during, and after injections of NGF (0.8 mM) or 5% NaCl into the gastrocnemius-soleus muscle. Of those neurones that reacted to NGF injections, most exhibited subthreshold excitatory postsynaptic potentials (EPSPs). Only a few reacted with action potentials (APs) at a low frequency. Five to 30 min after NGF, some cells showed signs of a sensitisation in that they now exhibited APs instead of EPSPs during electrical stimulation of the muscle nerve. 5% NaCl i.m. elicited APs in a significantly larger number of neurones and at a higher frequency (P<0.01). One day after NGF, the proportion of dorsal horn neurones responding with APs to electrical and mechanical stimulation had increased significantly (P<0.01). Despite the stronger excitatory effect of 5% NaCl, the responsiveness of the neurones was not significantly changed 1 day after 5% NaCl. In behavioural experiments on rats, NGF likewise had a stronger hyperalgesic action than 5% NaCl. The data demonstrate that low- frequency (or even subthreshold) input from muscle is an effective means of sensitising dorsal horn neurones.