The expression of fibronectin (FN) isoforms containing the extradomains A and B (ED-A+ and ED-B+ FNs) as well as a differentially O-glycosylated oncofetal form of the protein (onf-FN) was investigated in 6 normal human anterior pituitaries and 25 human pituitary adenomas. In normal tissue, immunohistochemical experiments showed the presence of FN molecules lacking the extradomains A and B (ED-A- and ED-B- FNs) without onf-FN immunoreactivity. These proteins were localized in the connective tissue compartment and especially in the vessel walls. Analysis of FN mRNA demonstrated an in situ synthesis of ED-A- and ED-B- FNs in the normal anterior pituitary. By contrast, in the adenomas, immunoreactivity for ED-A+ FN was observed in all cases. ED-B+ and onf-FN immunoreactivities were observed in 14 and 8 adenomas, respectively, regardless of the type, grade or invasiveness of the adenomas. ED-A+ FN mRNA was expressed in all adenomas studied, and ED-B+ FN mRNA was present in ED-B+ immunoreactive cases only. In pituitary adenomas, these 3 forms of FN were specifically associated with the endothelium and vascular smooth-muscle cells. Our results demonstrate that the processes of remodelling of the connective tissue compartment that occur in adenoma angiogenesis are associated with pre- and post-translational alterations of FN synthesis leading to the expression of ED-A+, ED-B+ and oncofetal FNs.