Twenty patients were studied prospectively during heparin therapy. Three activated partial thromboplastin time (APTT) reagents were used to compare APTT values with plasma heparin levels during induction of heparin and transition of heparin to coumadin. A heparin in vitro dose APTT response curve and a heparin ex vivo curve were established. The in vitro sensitivity curves using different reagents were varied at therapeutic heparin levels. In contrast, the APTT reagents did not differ ex vivo. The in vitro curves demonstrated poor performance. Sixty percent of the patients did not adequately compare by APTT estimation of plasma heparin levels. An APTT ratio (1.5 to 2.5) using the patient's baseline APTT as the denominator demonstrated better representation of heparin levels. The in vitro APTT curves are inappropriate for heparin monitoring.