The effects of polymers, dextran and polyvinylpyrolidone (PVP) and of albumin on the permeability of thrombin-induced fibrin networks developed in plasma were examined. Both PVP and dextran increased the network permeability and turbidity and increased the fibrin fibre thickness. The effect was molecular weight dependent. Derivation of the dimensionless permeability (permeability/fibre radius2) indicated that the increase in network permeability was mainly from altered arrangement of fibres and not from increased fibre thickness. The effects of albumin on network structure were similar to those of the polymers. Scanning electron microscopy of networks developed in plasma under the influence of dextran and poloxamer 188 showed fibres with increased thickness and a coarse nodular appearance. There was an increased tendency for fibres to be aggregated into clumps. It is suggested that during polymerization fibrin fibres and fibrin polymerization intermediaries behave as colloidal particles. Attractive forces between the particles are generated by soluble macromolecules such as plasma proteins or polymers. Attractive forces increase the thickness of fibrin fibres and induce a more permeable arrangement of the fibres in the network. The most likely colloidal mechanism is depletion flocculation. This would account for (1) the molecular weight dependence and concentration dependence of the effects of macromolecules, (2) the effects of macromolecules which do not bind to fibrin, (3) the effects of the surfactant poloxamer 188. Depletion flocculation may be a significant mechanism for biological regulation of fibrin network permeability by non-specific macromolecules such as soluble proteins or fibrin intermediaries.