The mitogenic response of Swiss 3T3 cells is regulated by synergistic interactions between multiple signal transduction pathways. Among the earliest nuclear signals in quiescent cells stimulated to divide is a dramatic increase in the expression of the c-fos proto-oncogene. The regulation of c-fos expression itself is a complex process involving several upstream enhancer elements which dictate the transcriptional response to specific intracellular signals. Here, we review our studies concerning the effects of defined molecular signals, alone or in combination, on c-fos mRNA levels in Swiss 3T3 cells. We propose that cell proliferation requires the cooperative interaction of distinct signalling pathways and that in this context c-fos induction plays a regulatory role in mitogenesis.