cDNA clones of human fos-related genes fra-1 and fra-2 were isolated by screening human c-DNA libraries with human fos DNA as a probe. We obtained human fra-1 cDNA clones that can code for a protein of 271 amino acid residues with a calculated molecular weight of 29,413 and showed 90% similarity with rat fra-1 protein. A new fos-related gene, fra-2, has one long open reading frame of 326 amino acids, and can code for a protein with a calculated molecular weight of 35,193. Two regions, a leucine zipper domain and C-terminal region, are conserved in the fos gene family. The fra-2 gene also harbors these two regions. Transcription of the fos, fra-1 and fra-2 genes was induced by phorbol ester (TPA) stimulation of U937 human monocytic cells. On TPA stimulation, the transcriptions of fos, fra-1 and fra-2 were detectable after 30, 60 and 120 min and maximum after 60, 90 and 240 min, respectively. These findings suggest that expression of the fos gene family is regulated by an orderly mechanism.