Ioxaglate, an iodinated contrast agent, decreases the rates of fibrin clot formation induced by thrombin or reptilase. This effect is not related to an increase in the ionic strength of the medium since a specific control of equivalent composition does not induce such variation. The concentration of ioxaglate which led to a 50% decrease of the control clot turbidity induced by thrombin was 17.5 +/- 2 mM. Macroscopically, clots formed with ioxaglate were larger and less turbid than the isotonic control. An increase in fibrin fibre diameters and a decrease in their densities were observed. During the fibrin polymerization process, all the fibrinogen was converted into fibrin, as for both the control and ioxaglate quantitative analysis of clots and supernatants showed (1) an identical quantity of FpA in clot supernatants, (2) the same quantities of protein incorporated into clots, and (3) no trace of fibrin monomers in the clot supernatants. Furthermore, dissolution in urea of clots formed in the presence of ioxaglate occurred more rapidly than in the control. Total incorporation of fibrinogen into clots, associated with a decrease in clot turbidity, indicated the existence of a qualitative abnormality in the construction of the three-dimensional fibrin structure. Using differential scanning calorimetry, it was observed that the two domains (D and E) of fibrinogen were modified by ioxaglate, showing the absence of specificity in the interaction between ioxaglate and a particular domain.