During the healing of an open wound, fibroblasts gradually become the main cellular elements of granulation tissue [Martinez-Hernandez, 19881, acquire morphological and biochemical features of smooth muscle (SM) cells, including the expression of a-SM actin, the actin isoform typical of vascular SM cells, and have been called myofibroblasts; they eventually disappear when granulation tissue evolves into a scar. Myofibroblasts persist in excessive scarring (hypertrophic scar) and in fibrotic conditions [for review, see Schurch et al., 19921. Thus wound healing and fibrocontractive diseases represent a useful model to study the synthesis and modulation of contractile proteins in a cell (ie, the fibroblast) in which they are expressed in low amounts or not expressed in resting conditions. In this review, we will first discuss the phenotypic heterogeneity of myofibroblasts in physiological and pathological situations; then we will examine the factors (cytokines and extracellular matrix components) which influence myofibroblast differentiation (and a-SM actin expression), and the interactions between myofibroblasts and other cellular elements.