1. When the hind limbs of the guinea-pig were perfused at constant volume inflow with undiluted pooled blood, an intra-arterial injection of the Forssman antibody caused a rapid and long-lasting pressor response.2. In the whole animal the pressor response was accompanied by a fall in the number of circulating platelets, but perfusion experiments suggest that serotonin was not responsible for the pressor response.3. When decomplemented serum was perfused through the hind-limb preparation the Forssman antibody failed to produce a rise in pressure, but a pressor response developed when unheated serum was subsequently introduced. This suggests that the actual combination of antibody with its tissue antigen is not the immediate cause of the pressor reaction.4. The cause of the pressor response is still unknown but apparently depends on the activation of the complement system. The effectiveness of serum shows that polypeptides split off from fibrinogen are not involved.