A remarkable range of activities has been ascribed to the family of proteins known as transforming growth factor-beta (TGF-beta). Each plays an important role in development and homeostasis, influencing mesenchymal-epithelial interactions, regulating cellular differentiation, and maintaining control of cell proliferation. Although in vitro comparisons of activity demonstrate a high degree of functional similarity, recent studies of mice with a targeted deletion of the TGF-beta1 gene reveal that true isoform-specific activities do exist in vivo and that the three mammalian isoforms are not functionally redundant. This approach has defined a unique role for TGF-beta1 in the establishment and maintenance of normal immune function, shed new light on the relevance of endogenous TGF-beta1 to the normal wound healing process, and expanded the list of known mechanisms of TGF-beta1 activity to include endocrine functions. Thus, the TGF-beta1-deficient mouse allows the definition of isoform-specific activities, providing an invaluable window through which to view the principal functions of TGF-beta1 in vivo.