We describe effects of serum insufficiency and cell contact on the transcription and abundance of the c-myc proto-oncogene mRNA in BALB/c 3T3 fibroblasts. In exponentially growing cells, withdrawal of serum caused a 10-fold decline in c-myc mRNA within 90 min. At least part of this decline was due to a decrease in the level of myc gene transcription. These cells became quiescent at subconfluence after 36-40 h. Cells made quiescent at subconfluence or confluence contained low levels of c-myc mRNA which rose more than 20-fold 2 h after stimulation of growth by fresh serum. Thereafter, the mRNA level declined. In subconfluent cells, it declined to the level in exponentially growing cells, i.e. nearly 10-fold over the level in quiescent cells. In confluent cells, by contrast, the mRNA returned to near-quiescent levels within 18 h (by mid-S phase). However, c-myc gene transcription was regulated identically in subconfluent and confluent cultures; quiescent cells transcribed c-myc at detectable levels, and stimulation by serum caused a 5-fold increase in 1 h, followed by a decline to about 2-fold over the quiescent level within 18 h. Thus, confluence affected steady state mRNA levels without affecting the level of transcription. Our results suggest that extracellular conditions that modulate cell proliferation (serum and cell contact) exert strong and rapid control over c-myc mRNA by post-transcriptional and transcriptional mechanisms.