The differentiation into macrophages of the U937 and HL60 human cell lines induced by 4 beta-phorbol 12-myristate 13-acetate (PMA) was accompanied by induction of the expression of the proto-oncogenes c-jun, jun B and jun D. However, expression of the three jun genes was regulated differently during induction of cell differentiation in both U937 and HL60 cells, with the three jun family members being expressed distinctly at different stages of cell differentiation. Whereas jun B transcription was strongly stimulated following treatment with PMA for 30 min, jun D mRNA levels were only increased 6 h after PMA treatment and the content of c-jun mRNA was elevated maximally only 24 h after PMA treatment. The rapid induction of the jun B mRNA level suggests a putative role for this proto-oncogene in the early triggering step of U937 and HL60 cell differentiation induced by PMA. Interestingly, a weak induction of jun B and jun D mRNA levels, but no induction of the c-jun mRNA level, was detected during Me2SO-induced granulocytic HL60 differentiation. These data suggest a different role for each jun proto-oncogene in regulating gene activity and that different transcriptional complexes involving distinct jun proto-oncogenes can be formed during macrophage and granulocytic differentiation.