The contribution of serotonin neurons to the functional recovery after spinal cord injury was studied pharmacologically in rats with moderately severe neurologic impairment (complete paraplegia but responsive to tail pinching) 24 h after thoracic spinal cord (T11) compression-induced injury. Fourteen days after cord injury the levels of endogenous norepinephrine (NE, -33%), dopamine (DA, -50%) and serotonin (5-HT, -55%) in the lumbar cord in the injury control rats were decreased and there were significant correlations between the neurologic score and the NE level (rs = 0.562, P less than 0.01) and the 5-HT level (rs = 0.745, P less than 0.001) but not the DA level. Bilateral i.c.v. injection of 5,7-dihydroxytryptamine (200 micrograms/rat) 24 h after cord injury significantly retarded the neurologic recovery during the 14 days after injury, accompanied by a further reduction in the 5-HT level (-86%) but not in the NE or DA level. On the other hand, neither p-chlorophenylalanine (PCPA) (300 mg/kg, i.p., once daily starting 24 h after injury for 13 consecutive days) nor reserpine (1 mg/kg, i.p., 4 times, once 24 h after injury and then every fourth day) had any influence on the time course of the neurologic recovery during the 14 days after injury, although PCPA treatment further reduced the levels of NE (-50%) and 5-HT (-91%), and reserpine treatment further reduced the levels of NE (-95%), DA (-73%) and 5-HT (-85%).(ABSTRACT TRUNCATED AT 250 WORDS)