The physiological derangements during and following the administration of higher oxides of nitrogen have been studied in dogs anaesthetized with pentobarbitone. The dogs were exposed to concentrations of nitric oxide or nitrogen dioxide between 0.1 and 2.0 per cent over periods between 5 and 136 minutes. Despite the inhalation of 98 per cent oxygen, death was always associated with a critical reduction in arterial oxygen content. This was caused by one or more of the following three factors: methaemoglobinaemia, low arterial Po2, and acidaemia which caused a shift of the oxyhaemoglobin dissociation curve. The reduction of arterial Po2 was caused by an outpouring of fluid into the alveoli.