The effects of cyproheptadine on locomotion and on spasticity in patients with spinal cord injuries. The effects of cyproheptadine, a serotonergic antagonist, were studied in seven patients with spastic paresis of spinal origin. Six patients were included in a double blind crossover trial (maximal dose 24 mg/day). The patients were evaluated on both their spasticity and locomotor function. Four of the patients also participated in an open trial in which cyproheptadine was administered for a minimum of six months at optimal dose. Patients walked on a treadmill at full weight bearing when possible, or with 40% of their body weight externally supported, as required, by an overhead harness system. Cyproheptadine considerably decreased the sustained ankle clonus and episodes of spontaneous spasms observed in all the patients who previously presented these manifestations of spasticity. Two patients who required body weight support (BWS) during locomotion could walk at full weight bearing during cyproheptadine therapy. A more normal timing of EMG patterns in these patients during cyproheptadine therapy was associated with temporal distance changes and marked improvement of joint angular displacement. In contrast, the other patients showed marginal changes in the EMG and the kinematic pattern but eventually managed to walk at a higher speed. These preliminary results suggest that cyproheptadine can reduce spasticity and enhance locomotor function in spinal cord injured patients. 