The three high molecular weight (HMW) forms of fibroblast growth factor- 2 (FGF-2) have a distinct intracellular localization and differentially affect cell mobility and growth compared with the fourth 18-kDa form. To characterize further the effects of the 18-kDa and HMW forms of FGF-2, we have examined their ability to modulate integrin expression. Transfected NIH 3T3 cells expressing only 18-kDa FGF-2 exhibited increased cell surface levels of α5β1, whereas cells expressing only HMW FGF-2 exhibited cell surface α5β1 levels similar to parental cells. When cells synthesizing 18- kDa FGF-2 were transfected with a cDNA encoding a dominant negative FGF receptor, α5β1 cell surface levels decreased. Immunoprecipitation of biosynthetically labeled cells indicated that expression of 18-kDa FGF-2 increased the biosynthesis and rate of maturation of α5. Northern blot analysis showed that 18-kDa FGF-2 increases the level of the α5 subunit mRNA but does not affect β1 subunit transcript levels. Experiments utilizing luciferase reporter gene activity revealed increased α5 promoter activity in cells expressing 18-kDa FGF-2 indicating that the enhanced α5 transcript level is due to modulation of the transcription rate. Therefore, interaction of 18-kDa FGF-2 with FGF receptors results in changes in α5β1 biosynthesis and processing. In contrast, endogenous expression of HMW FGF-2 does not mediate this effect.