Histologic evaluation of endomyocardial biopsy specimens is the current method of monitoring rejection after cardiac transplantation. Unfortunately, this technique gives a discontinuous evaluation of the recipient immunologic status. A noninvasive marker of immunologic activation and of allograft rejection that would permit a more continuous monitoring than the biopsy technique would be clinically useful. Urinary polyamine excretion reflects cellular proliferation or degeneration and, as a marker of cellular metabolic activity, may also reflect lymphocyte proliferation and organ rejection. From July 1985 to December 1986, urinary polyamines were studied in 18 patients during hospitalization for heart and heart-lung transplantation. Endomyocardial biopsy was performed twice a week and histologic rejection was characterized by standard criteria. Urinary specimens were collected daily and analyzed for polyamines by high-pressure liquid chromatography. Concentrations of acetylputrescine and total urinary polyamines were significantly higher before the 20 rejection episodes than before the 80 biopsies yielding negative results. So that their clinical usefulness could be evaluated, an elevation of polyamines and a daily level variability of 28% or more was chosen to indicate increased metabolic cellular activity and to predict rejection in the next 8 days. On the basis of these definitions, the sensitivity of polyamine assays to predict rejection was 85%, the specificity 88%, and the positive predictive value 79%. Therefore, serial measurements of urinary polyamines may provide daily information on the recipient's immunologic status after cardiac transplantation.