The effects of serotonergic substances on the locomotor pattern and cutaneous reflexes were studied in 3 adult chronic spinal cats trained for 1-3 months to walk with their hindlimbs on a treadmill. The 5-hydroxytryptamine (5-HT) precursor, 5-hydroxytryptophan (5-HTP), and two 5-HT agonists, 5-methoxy-N,N-dimethyltryptamine and quipazine, were found to generally increase the step length and augment the amplitude of hindlimb extensors and flexors as well as axial muscles. Correspondingly, the excursion of the hip, the knee and the ankle joints was increased, mainly in the flexion direction. Cyproheptadine, a 5-HT antagonist, partially or completely antagonised these effects. The threshold current needed to elicit a flexion reflex by stimulating the dorsum of the paw through implanted wires, was lower after the injection of 5-HT agonists than in the immediately preceding control period. Fast paw shaking initiated by dipping the paw in water was unchanged after quipazine and was not abolished by cyproheptadine. In accordance with others, our results suggest that serotonergic drugs may increase the excitability of several types of spinal neurones, including motoneurones, and consequently influence the locomotor pattern as well as the reflex responsiveness. The changes observed with serotonergic agonists were different in many respects from those obtained with noradrenergic agonists and these differences are discussed. This may indicate specific roles for these classes of substances on locomotor function and reflex activity and also provide a basis for further clinical investigations.