During pregnancy stretch of the uterus, imposed by the growing fetus, is an important signal for the induction of genes involved in the onset of labor. In this study the expression of activator protein-1 (AP-1) family mRNAs in response to in vitro stretch was investigated in myometrial cells. Rat primary myometrial smooth muscle cells were plated onto collagen I coated Flex I culture plates and subjected to 25% static stretch on day 4 of culture. Static stretch-induced an increase in the expression of c-fos, fosB, fra-1, c-jun and junB. The expression of both c-fos and junB was maximally induced at 30 min by static stretch. The peak induction for fosB and c-jun occurred at 1 hr, whereas the peak of fra-1 induction occurred between 1 and 2 hrs after application of stretch. Treatment of myometrial cells with progesterone (100 nM, 400 nM, 1 µM) for 1 or 6 hrs before the application of static stretch, did not affect the magnitude of the c-fos response. However, 24 hr of progesterone exposure reduced the magnitude of c-fos and fosB stretch induction at both the 400 nM and 1 µM dose. These data indicate that several members of the AP-1 family are stretch responsive genes in myometrial smooth muscle cells. This response can be attenuated by pre-treatment with progesterone, however, the requirement for longer pre-treatment times suggests that the inhibitory actions of progesterone do not occur through a direct action of the progesterone receptor within the promoter regions of AP-1 genes.