A number of noradrenaline and serotonin agonists were tested to investigate which of them replicate the depressive actions of monoamines on transmission from group II muscle afferents in the cat spinal cord. The agonists were applied ionophoretically at the two sites at which maximal monosynaptic focal field potentials are evoked from group II afferents-in the intermediate zone and the dorsal horn of the 4th and 5th lumbar segments. Their effects were estimated from changes in the amplitude of the field potentials. The compounds tested fell into three categories according to the site at which they depressed transmission from group II afferents: one category with highly selective actions in the intermediate zone, a second category with similarly selective actions in the dorsal horn, and a third category with non-selective actions. Drugs in the first category included three noradrenaline agonists (tizanidine, B-HT 933 and clonidine), included in the second were five serotonin agonists (8-OH-DPAT, 5-methoxytryptamine, alpha-methyl serotonin, DOI and 2-methyl-serotonin), and in the third two noradrenaline agonists (phenylephrine and isoproterenol) and two serotonin agonists (RU 24969 and 5-carboxamidotryptamine). Field potentials evoked by group I afferents remained unaffected by all but one compound (8-OH-DPAT). Effects of one noradrenaline agonist and one serotonin agonist (tizanidine and 5-methoxytryptamine) were also tested on responses of single extracellularly recorded neurons. Tizanidine depressed responses induced by stimulation of group II afferents in intermediate zone interneurons, but not in dorsal horn neurons, while 5-methoxytryptamine depressed activation of the latter. Tizanidine had no effect on responses evoked by group I afferents, either in intermediate zone interneurons or in the dorsal spino-cerebellar tract neurons of Clarke's column. It is hypothesized that noradrenaline and serotonin released by descending monoaminergic neurons differ in the potency with which they depress transmission from group II afferents to different functional types of neuron. The results suggest that this depression may involve different membrane receptors at different locations, primarily alpha2 adrenoceptors in the intermediate zone/ventral horn and 5-HT1A serotonin receptors in the dorsal horn.