The literature suggests that platelets might help mediate the pulmonary vascular pressor response to hypoxia. This study evaluated the hypoxic response in thrombocytopenic dogs. Platet depletion was achieved in five dogs by the use of platelet antiserum. In the normoxic state these dogs had lower cardiac outputs and higher pulmonary and systemic vascular resistances than five control dogs. The pressor response to hypoxia in these dogs was not only preserved but considerably enhanced in comparison to the control dogs. Hypoxia increased the pulmonary vascular resistance 146 +/- 17% above its normoxic value in the thrombocytopenic dogs and 64 +/- 21% in the control dogs. Thus platelets may normally produce a dilator substance or inactivate a pressor substance during hypoxia. The mechanism of the effect is not apparent but it is clear tha the pulmonary pressor response to hypoxia in the dog is not mediated by platelets.