Long-term response to vasodilator therapy was assessed in six patients with PPH. Following an acute trial, each patient was restudied after (1) two months of drug administration, (2) one month of abstinence from therapy, and (3) an additional two months of therapy. Three of six patients had no long-term reduction of PVR after treatment; one showed a progressive increase. Of the three patients whose PVR was still reduced at the end of the second therapy period none showed a return of PVR to baseline during the abstinence phase, which may suggest that long-term reduction of pulmonary vascular tone may modify the vasoconstrictive component of this disease. The heterogeneous response of this small number of patients to sequential drug administration and withdrawal demonstrates the difficulty of interpreting previously reported clinical trials and underscores the need for a well-designed controlled study of vasodilator administration in these patients.