We investigated whether ET-1 is synthesized by and released from mesangial cells. ET-1-like immunoreactivity (LI) released into medium increased time-dependently under a serum-free condition. The amounts of ET-1-LI released into the medium was augmented in the presence of fetal calf serum. Reverse-phase HPLC profile of the conditioned media revealed a major component coeluting with standard ET-1. Northern blot analysis of poly(A) +RNA extracted from mesangial cells showed a single major band corresponding to the size of preproET-1 mRNA (2.3 kb). These findings demonstrate that ET-1 is synthesized by and released from rat mesangial cells and suggest a possibility that it acts on their own cells as an autocrine factor.