To investigate changes in the growth hormone binding protein (GH-BP) in renal disease, gel chromatography was used to separate free and bound hormone after incubation with 125I-GH, the results being expressed as a percentage of radioactive GH eluting in a high molecular weight (70-80 kD) peak. In 26 normal individuals, binding was 39.3 +/- 8.0%, while in 11 patients with renal disease who were off dialysis binding was reduced to 16.8 +/- 5.6%. Similarly, in 9 patients undergoing hemodialysis binding was reduced to 24.6 +/- 6.8%, in 8 patients undergoing chronic ambulatory peritoneal dialysis binding was reduced to 25.7 +/- 7.6%, and in 9 patients within three months of a renal transplant binding was reduced to 25.1 +/- 8.6%. Scatchard analysis showed that these changes were not a result of decreased affinity of GH-BP for GH, and receptor binding studies showed that uremic serum was not inhibiting binding. The decreased concentration of GH-BP may indicate decreased expression of the GH receptor in target tissues, and hence diminished responsiveness to GH in renal failure.