Many questions remain concerning the precise mechanism by which the luminal signal for renin secretion is transmitted from the MD to the JG granular cell. It appears likely that a number of pathways may participate in MD-mediated changes in renin release, some of the agents serving to modulate release, others participating directly in signal transmission. Collectively, the current information suggests a transmission pathway that involves several steps. First, changes occurring in MD NaCl transport, which result directly from alterations in luminal NaCl concentration, act to initiate the response. Second, conveyance of this signal to the extraglomerular mesangial cells via a change in the ionic environment of the EGM field and/or a paracrine factor produced by the MD (perhaps NO) appear likely to be the next step. The subsequent steps probably include changes in prostaglandin production by the EGM, and possible participation of other paracrine factors produced by both endothelial and extraglomerular mesangial cells.