Recent evidence suggests that epidermal growth factor (EGF) may serve as a paracrine and/or autocrine mediator of oestrogen action in uterine growth. In this study, the effects of various steroid hormones on EGF receptors in primary cultures of human endometrial cells were examined. Human endometrial cells exhibited a single class of high-affinity binding sites for EGF (Kd: 0.14 nM) with approximately 3600 receptors/cell. The addition of progesterone increased the EGF binding without affecting the Kd value. Cortisol also increased EGF binding and acted additively with a relatively low concentration of progesterone (10(-10) M). Oestradiol alone had no effect on EGF binding. However, oestradiol in combination with progesterone and cortisol further increased EGF binding. These results present evidence for the direct regulation of EGF receptors by steroid hormones in human endometrial cells, and raise the possibility that steroid hormones may act on these cells in part by modulating EGF receptors.