Human GH (hGH) secretion is stimulated by vigorous physical activity, whereas immobilization reduces its release. In paralyzed subjects with spinal cord injury (SCI), it has recently been shown that the release of hGH to provocative stimulation and plasma insulin-like growth factor-I (IGF-I) levels are reduced. The acute administration of baclofen, a gamma-aminobutyric acid derivative, has been shown to stimulate hGH release. The present study investigated the effect of chronic administration of baclofen on the provocative testing of hGH secretion and plasma IGF-I levels. Sixteen subjects with SCI were studied; eight subjects were treated (40-80 mg/day; > 6 months) with baclofen (Bac+), and eight were not (Bac-). Additionally, 8 non-SCI subjects were studied as controls. The groups were matched for gender and age. The subjects were not receiving any medications known to influence hGH secretion. After an overnight fast, arginine hydrochloride (30 g/subject) was infused iv over 30 min, with blood drawn for hormone determinations at baseline and 30, 60, 90, and 120 min. In the Bac- group compared with the Bac+ group, the arginine-stimulated mean plasma hGH levels at 30 and 60 min (P < 0.05) and peak and sum plasma hGH levels (P < 0.01) were reduced. There were no significant differences in the plasma hGH response between the Bac+ group and the control group. Plasma IGF-I levels may reflect the integrated tissue response to hGH. A significant inverse relationship was present between age and plasma IGF-I levels for the control and Bac+ groups, but not for the Bac- group. The mean plasma IGF-I level was significantly reduced in the Bac- compared with the Bac+ group. No significant differences in mean plasma IGF-I levels were noted between the Bac+ and control groups. SCI is associated with body composition changes and metabolic alterations that may be exacerbated by reduced activity of the hGH-IGF-I axis. Oral chronic baclofen therapy appears to reverse the deleterious effects of paralysis and immobilization on hGH physiology.