Plasma norepinephrine (PNE) levels are significantly elevated in patients with endstage congestive heart failure. To assess whether this abnormality is reversible, 32 patients were studied before and 3 to 9 months after orthotopic cardiac transplantation. PNE decreased after the transplant procedure form 739 +/- 363 to 301 +/- 161 pg/ml (p less than .05). In 13 patients, PNE was measured sequentially during the first 3 months after the transplant procedure. PNE decreased from 590 +/- 293 to 321 +/- 208 pg/ml at 2 weeks and remained stable at 1 month (308 +/- 239 pg/ml), 2 months (307 +/- 196 pg/ml), and 3 months (331 +/- 131 pg/ml), even while arterial hypertension developed. No correlation was found between PNE, systolic, diastolic, or mean arterial pressure and cyclosporine A blood levels. These data demonstrate that normalization of plasma levels of norepinephrine occurs shortly after cardiac transplantation in man. This decrease in PNE is probably independent of immunosuppression therapy. Finally, the development of arterial hypertension in cyclosporine A-treated cardiac transplant patients is not due to activation or persistent activation of the sympathetic nervous system.