The effect of fetal-calf serum (FCS) and Forskolin (FKN) on cholecystokinin (CCK) and proto-oncogene c-fos mRNA expression in the human neuroblastoma cell line SK-N-MC, cultured in serum free medium was studied by Northern blot analysis and nuclear run-off transcription analysis. Addition of FCS or FKN gradually increased the basal CCK mRNA level approximately four to six-fold after 2-4 h. In contrast, a strong and transient increase of the c-fos mRNA-level was observed, approximately forty to fifty-fold after 50-60 min over unstimulated cells. Nuclear run-off transcription analysis indicates that c-fos mRNA is constitutively expressed and transcription may be further stimulated by FCS and FKN. Moreover, in SK-N-MC nuclei, transcription of the c-fos gene clearly precedes stimulated CCK-mRNA expression. This suggests that FOS, which is known to form a AP-1 heterodimer transcription complex with the proto-oncogen product, Jun, may bind to the tentative AP-1 binding site, found within the human CCK promoter and thereby modulates basal and enhanced CCK-mRNA expression in SK-N-MC cells.