The present study was undertaken to examine vasopressin gene expression in response to a normal versus hypertonic sodium chloride (506 mOsm/kg H2O) intake for 7 days in Sprague-Dawley rats. The animals in both groups demonstrated precision in maintaining constancy of body fluid composition in spite of large differences in sodium and water intakes. Compared with the rats on a normal diet, chronic ingestion of hypertonic sodium chloride resulted in significant increases in total fluid intake (210 ± 8 mL v 471 ± 48 mL, P < 0.001) and total urine output (86 ± 5 mL v 347 ± 48 mL, P < 0.001), while glomerular filtration rate, hematocrit, serum urea nitrogen, creatinine, serum sodium, and plasma osmolality were unchanged. Without detectable changes in plasma osmolality or intravascular volume, vasopressin release from the pituitary, as measured by plasma and pituitary vasopressin concentrations (1.5 ± 0.1 pg/mL v 5.9 ± 1.5 pg/mL, P < 0.01 and 2.0 ± 0.5 μg/pituitary v 0.86 ± 0.1 μg/pituitary, P < 0.01, respectively), was increased in the animals ingesting hypertonic sodium chloride. In addition, vasopressin gene expression as measured by hypothalamic vasopressin mRNA concentrations was significantly increased 1.85-fold (P < 0.001) in the animals ingesting hypertonic sodium chloride. In summary, Sprague-Dawley rats ingesting hypertonic sodium chloride (506 mOsm/kg H2O) were able to maintain sodium and water homeostasis over a 7-day period. Yet, in these animals plasma vasopressin increased, pituitary vasopressin stores decreased, and hypothalamic vasopressin gene expression was stimulated. These findings in the rat therefore implicate exquisite sensitivity for both vasopressin synthesis and secretion in response to a chronic hypertonic stimulus. © 1993, National Kidney Foundation. All rights reserved. All rights reserved.