Fibronectin is a ubiquitous glycoprotein found in plasma, on the surface of a number of cell types and in the extracellular matrix. It is believed to function as an adhesive protein for cells by mediating their interaction with connective tissue macromolecules. This study uses the rotary shadowing technique to investigate the interaction between human plasma fibronectin and native calf skin type I collagen molecules. Purified human plasma fibronectin appears fibrillar with a total length of 152 +/- 48 nm (n = 127). Individual molecules of fibronectin interact with one another in an apparent concentration dependent process to form linear polymeric structures up to 10 molecules by end-to-end association. Incubation of various concentrations of fibronectin with collagen results in the interaction of fibronectin with specific sites on the native collagen molecules. In addition, polymeric forms of fibronectin interact with collagen molecules and occasionally bridging structures between collagen molecules are formed. This study provides direct visual demonstration of an interaction between fibronectin and native collagen molecules. Possible physiologic implications of these observations are discussed.