We describe a patient with biopsy-proven pulmonary talc granulomas (secondary to the long-term intravenous injection of crushed tablets of pentazocine) who had two episodes of transient pulmonary hypertension following the injection of this oral medication. We established a canine model and measured the right lymph duct flow, mean pulmonary arterial pressures, and pulmonary vascular resistance to determine the short-term effects on hemodynamics and the flow of lymph after intravenous administration of crushed pentazocine tablets (3 to 4 mg/kg of body weight) or pure talc (2.5 to 3 mg/kg). A typical response to both agents consisted of short-term elevations of mean pulmonary arterial pressure and pulmonary vascular resistance to approximately twice baseline values, with a slow decrement over 30 to 45 minutes. The average flow of lymph tripled, peaking at approximately two hours after injection. The lymph contained high levels of albumin. We concluded that the talc filler in oral tablets of pentazocine induces the pulmonary hypertension, probably by mechanical obstruction of the pulmonary vasculature. Association with this transient pulmonary hypertension is an increase in the permeability of the pulmonary microvasculature.