This mini-review by Daniel B. Rifkin and David Moscatelli focuses on recent developments in the cell biology of basic fibroblast growth factor (bFGF). The authors highlight several areas where uncertainties remain in bFGF biology, particularly in its synthesis, distribution, biological activities, related proteins, transforming potential, receptors, release, and interactions with the extracellular matrix (ECM). Key points include: 1. **Synthesis**: bFGF is synthesized without a signal sequence, leading to questions about its intracellular localization and release mechanism. Multiple forms of bFGF are generated through translation initiation at both CUG and AUG codons, suggesting different functional roles. 2. **Distribution**: bFGF is found in all organs, tissues, tumors, and cultured cells, but its ubiquitous distribution in cultured cells may be artifactual. In vivo distribution is more restricted. 3. **Biological Activities**: bFGF displays a broad spectrum of activities, including increased growth, induction of plasminogen activator, collagenase, and cell migration. It also plays a role in neovascularization and wound repair, and may act as an embryonic inducer. 4. **Related Proteins**: bFGF is part of a family of related proteins, including hst/K-fgf and FGF-5, which share receptors and may have overlapping affinities. 5. **Transforming Potential**: High expression of bFGF can transform cells, but the amount required is high, and the mechanism of transformation is unclear. 6. **Receptors**: bFGF receptors have been identified on various cells, with binding affinity estimated at 2 × 10^-11 M to 2 × 10^-10 M. The number of receptors per cell varies, and they are down-regulated by endogenous growth factors. 7. **Release**: The mechanism of bFGF release is not well understood. It may be released via cell death or through heparinase or plasmin action, which can also protect bFGF from degradation. 8. **Matrix Interactions**: bFGF strongly interacts with heparin and the ECM, possibly through heparan sulfate proteoglycans (HSPG). This interaction may provide a reservoir of growth factor and contribute to its long-term activity. The authors conclude that bFGF has unique properties, such as its lack of a signal sequence and intracellular localization, which suggest a novel mode of action. The interaction of bFGF with the ECM may represent a new type of extracellular functional control.This mini-review by Daniel B. Rifkin and David Moscatelli focuses on recent developments in the cell biology of basic fibroblast growth factor (bFGF). The authors highlight several areas where uncertainties remain in bFGF biology, particularly in its synthesis, distribution, biological activities, related proteins, transforming potential, receptors, release, and interactions with the extracellular matrix (ECM). Key points include: 1. **Synthesis**: bFGF is synthesized without a signal sequence, leading to questions about its intracellular localization and release mechanism. Multiple forms of bFGF are generated through translation initiation at both CUG and AUG codons, suggesting different functional roles. 2. **Distribution**: bFGF is found in all organs, tissues, tumors, and cultured cells, but its ubiquitous distribution in cultured cells may be artifactual. In vivo distribution is more restricted. 3. **Biological Activities**: bFGF displays a broad spectrum of activities, including increased growth, induction of plasminogen activator, collagenase, and cell migration. It also plays a role in neovascularization and wound repair, and may act as an embryonic inducer. 4. **Related Proteins**: bFGF is part of a family of related proteins, including hst/K-fgf and FGF-5, which share receptors and may have overlapping affinities. 5. **Transforming Potential**: High expression of bFGF can transform cells, but the amount required is high, and the mechanism of transformation is unclear. 6. **Receptors**: bFGF receptors have been identified on various cells, with binding affinity estimated at 2 × 10^-11 M to 2 × 10^-10 M. The number of receptors per cell varies, and they are down-regulated by endogenous growth factors. 7. **Release**: The mechanism of bFGF release is not well understood. It may be released via cell death or through heparinase or plasmin action, which can also protect bFGF from degradation. 8. **Matrix Interactions**: bFGF strongly interacts with heparin and the ECM, possibly through heparan sulfate proteoglycans (HSPG). This interaction may provide a reservoir of growth factor and contribute to its long-term activity. The authors conclude that bFGF has unique properties, such as its lack of a signal sequence and intracellular localization, which suggest a novel mode of action. The interaction of bFGF with the ECM may represent a new type of extracellular functional control.