The fps/fes proto-oncogene encodes a cytoplasmic protein tyrosine kinase that is thought to participate in signaling pathways involving members of the cytokine receptor superfamily, including those for erythropoietin, granulocyte-macrophage colony-stimulating factor, leukemia inhibitory factor, oncostatin M, ciliary neurotropic factor, and interleukins 3, 4, 6, and 11. Expression of fps/fes has been detected in hematopoietic cells, vascular endothelial cells, and cell types arising from all three germ layers during early development. Here, we describe fps/fes expression in developing and adult tissues from normal mice or from transgenic animals overexpressing wild-type or activated mutant fps/fes alleles. The highest levels of fps/fes expression were seen in angioblasts of early yolk sac blood islands, chondrocytes, vascular endothelial cells, neuronal cells, and several epithelial cell types, including those of the choroid plexus and the uterus. Fps/Fes protein was concentrated in the perinuclear region of cultured neuronal, myeloid, epithelial, and vascular endothelial cells, and a chimeric Fps/Fes-green fluorescence protein colocalized with gamma-adaptin, a marker for the trans-Golgi apparatus. These observations suggest the involvement of Fps/Fes in vesicle transport processes in cells with prominent secretory functions.