Spaceflight or hindlimb suspension results in a loss of mass and alterations of the metabolic and contractile protein profiles of skeletal muscles toward that resembling faster muscles. Given the influence of motoneurons on muscle properties, ventral horn cells of the lumbosacral enlargement of the spinal cord were studied to determine whether similar adaptations were present. Three groups of rats (5 per group) were studied: control, 14-day spaceflight, and 14-day hindlimb suspension. Spinal cords were quick-frozen, and the succinate dehydrogenase (SDH) activity and cross-sectional area of the soma of ventral horn cells were measured using a computer-enhanced image-processing system. Briefly, the optical density for SDH activity was determined after 8 min of incubation in a medium that gave a steady-state enzymatic reaction. Soma sizes were determined in cells with a visible nucleus. Although there were no significant differences among the three groups in mean cross-sectional area and SDH activity, the population distributions of both variables shifted significantly. In the flight rats, there was a shift toward smaller cells. Compared with control, the population distribution of SDH activities in the flight rats shifted toward higher activities, whereas the distribution shifted toward lower activities in the suspended rats. When considering the interactive effects within individual cells, there was a higher percentage of small cells with high SDH activities in the flight than in the control or suspended rats. These contrasting effects of spaceflight and hindlimb suspension suggest that the changes observed in ventral horn cells were due to factors other than simply the absence of weight support.