Many studies have shown that vigorous exercise acutely stimulates growth hormone (GH) release but the relative contribution of daily physical activity to maintaining the GH/somatomedin C (SmC) axis is not known. It has been reported that basal and post-exercise plasma SmC values are higher in physically conditioned young men than in sedentary men of similar age. To assess the effect of severe inactivity on the plasma SmC level, basal concentrations of this hormone were measured in patients with quadriplegia (QP) resulting from spinal cord injury (SCI). Venous blood samples were obtained after overnight fast in 41 QP men, ages 24-66, and compared with 119 healthy men of similar ages. Nonparametric analysis of variance showed SmC to be significantly lower in QP than in healthy men (p < .007). Plasma SmC below 0.35 U/ml in adults usually indicates little or no GH secretion by the pituitary gland. In QP, 46% of plasma SmC values were < 0.35 U/ml compared to 24% in the healthy group (p < .02). In both groups, an inverse relationship of SmC and increasing age was observed (p < .01). The data suggest that severe inactivity or SCI tend to cause hyposomatomedinemia. The latter endocrine alteration may contribute to the decrease in lean body mass and muscle atrophy of QP patients, and add further functional impairment to the original neurologic deficit. In addition, hyposomatomedinemia could increase the tendency for pressure sore formation and osteoporosis in SCI patients.