Our object was to see whether the action of hypoxia on pulmonary blood vessels is due to release of a mediator like Mstamine. 30 male subjects in the age group 20–30 years were selected for this study. They were divided into three groups with 12 men in each group. The first group included those who had pulmonary oedema of high altitude (POHA) sometime back. The second group included those who never suffered from POHA in spite of their stay at high altitude for over 2 years. The third group consisted of men who had never been to the heights. Basal arterial plasma histamine levels were estimated in all the subjects by the method of Huff et al. The same estimation was done in samples of blood taken 10 min after hypoxic breathing for each subject. It was found that the basal histamine levels were more or less the same in all the three groups. After hypoxia there was significant rise in plasma histamine levels in all the three groups. There was no significant difference in the rise in the histamine levels on comparing the values for the three groups. It is postulated that the significant rise in plasma histamine levels is responsible for the rise in pulmonary vascular resistance. It is also postulated that the rise in pulmonary vascular resistance is dependent more on the reactivity of the pulmonary arterioles rather than on the amount of histamine released. Hyperreactivity of the pulmonary vasculature is the factor that determines the degree of vascular constriction and consequent development of POHA.