Neurite outgrowth from chick dorsal root ganglia entrapped in isotropic and magnetically aligned fibrin gels was studied, and the dependence on the diameter of the fibrin fibrils was characterized. The fibrin fibril diameter was varied, as inferred from turbidity measurements, by using different Ca2+ concentrations in the fibrin-forming solution, but this variation was accomplished without affecting the degree of magnetic-induced alignment, as directly visualized in fluorescently spiked gels. Magnetically aligned fibrin gels possessing different fibril diameters but similar alignment resulted in drastic changes in the contact guidance response of neurites, with no response in gels formed in 1.2 mM Ca2+ (having smaller fibril diameter, ca. 150 nm), but a strong response in gels formed in 12 and 30mM Ca2+ (having larger fibril diameter, ca. 510 nm) with an attendant two-fold increase in neurite length. These changes are attributed to variation of the mechano-structural properties of the network of aligned fibrils as the fibril diameter is varied. (C) 2001 Elsevier Science Ltd. All rights reserved.