We measured the serum GH responses to GHRH (1 micrograms/kg) in six normal men who had been rendered hyperinsulinemic and hypolipidemic by 10 days of total parenteral nutrition (TPN subjects) with a 25% dextrose-amino acid solution. The men underwent GHRH testing after 3 h of infusion of NaCl or Met-human (h) GH (2 micrograms/kg.h). The results of these tests were compared with those of five men tested in the post-absorptive state (PA subjects). The serum GH response to GHRH during NaCl infusion was significantly lower in the TPN subjects than in the PA subjects. During the Met-hGH infusion, the serum GH response to GHRH in the PA subjects was significantly lower than that after the NaCl infusion, whereas in the TPN subjects the response was similar to that during the NaCl infusion. The mean integrated areas under the GH response-time curve after GHRH treatment were 3963 +/- 2086 min/micrograms.L following NaCl infusion and 413 +/- 64 min/micrograms.L following Met-hGH infusion in PA subjects; they were 1127 +/- 500 min/micrograms.L following NaCl infusion and 1456 +/- 682 min/micrograms.L during Met-hGH infusion in the TPN subjects. The Met-hGH infusions resulted in a significant increase in serum FFA concentrations in the PA, but not the TPN, subjects. These results suggest that hyperalimentation induces a metabolic background which inhibits GH secretion, as manifested by a diminished serum GH response to GHRH administered after NaCl infusion. The absent FFA response to Met-hGH infusion in the TPN subjects may explain why the Met-hGH infusion in them did not result in a reduced serum GH response to GHRH as occurred in the PA subjects. Hence, FFA may play an important role in the effects of short term Met-hGH infusion on GH secretion.