unpaired (upd) encodes a ligand for the Jak/STAT signaling pathway in Drosophila. In the second instar and early third larval eye disc, upd is expressed in the center of the posterior margin. upd loss-of-function mutations caused eye size reduction and upd overexpression caused eye enlargement. Upd regulates eye size through the Dome/Jak(Hop)/STAT92 signaling pathway to promote cell proliferation. Interestingly, the effect of Upd is only on cells located anterior to the morphogenetic furrow (MF), but has no effect on the second mitotic wave, which is posterior to MF. Overexpression of upd behind MF can nonautonomously induce cell proliferation up to 20 rows of cells anterior to MF. The G1 cyclin, cycD transcript level was also enhanced anterior to MF. Consistent with the long-range effect, we found that the extracellular Upd protein can be detected over a comparable long range, suggesting that Upd acts directly over a long distance as a signaling molecule.