The interactions between different doses of serotonin (5-HT) and norepinephrine (NE) in in vivo experiments on rat spinal cord dorsal horn cells was investigated using the integrated electromyography (EMG) measurement of the nociceptive hindlimb flexor reflex (FR). The results indicate that (1) intrathecal (IT) administration of low doses of 5-HT (60 nmol) or NE (1.5 nmol) suppresses the nociceptive FR by 40% for 20 min, respectively; (2) administration of higher doses of 5-HT (240 nmol, IT) multiplies the suppression of the nociceptive FR by 80% for 40 min, and NE (15 nmol, IT) produces similar suppression of the nociceptive FR for 80 min; (3) concomitant administration of low doses of 5-HT (60 nmol, IT) and NE (1.5 nmol, IT) produces a summation of the nociceptive FR suppression both in amplitude and duration; (4) concomitant administration of the higher doses of 5-HT (240 nmol IT) with NE (15 nmol, IT) produces similar effect obtained as 5-HT given separately, and no summation was obtained as observed following the lower dosages; (5) serotonin (240 nmol, IT) given 40 min before NE (15 nmol, IT) attenuates the duration of the suppression induced by NE; (6) pretreatment with a selective 5-HT2 receptor antagonist ketanserin (60 nmol, IT) failed to abolish the 5-HT effects; (7) pretreatment with ketanserin prior to concomitant administration of the higher doses of 5-HT and NE prolongs the time duration of the nociceptive FR suppression.(ABSTRACT TRUNCATED AT 250 WORDS)