Radiologic contrast materials activate complement by both the classical and alternative pathways. This activation is time, dose, and temperature dependent and is able to proceed with equal facility in either the presence or absence of Ca++ or Mg++ chelating reagents (EGTA, EDTA). All the components examined (C1, C4, C2, Factor B, C3, and C5) were consumed during complement activation. Immune complexes are produced during interaction of serum with contrast materials. The activation of complement by contrast materials appears to be principally initiated by the activation of plasminogen to plasmin. Inhibition of plasminogen activators by epsilon-aminocaproic acid affects complement activation markedly.