The expression and secretion of different isoforms of transforming growth factor-beta (TGF beta) were examined in cultured transformed and nontransformed human retinal pigment epithelial (RPE) cells. Transformed RPE cells were found to express high levels of TGF beta 1 mRNA, low levels of TGF beta 3 mRNA but no detectable TGF beta 2 mRNA. If the cells were grown under serum-free conditions the expression of TGF beta increased. The mRNA expression was accompanied by secretion of TGF beta 1 (but not TGF beta 2) protein into the culture media. By comparison, nontransformed RPE cells were found to secrete similar amounts of TGF beta as transformed cells but predominantly secreted TGF beta 2. The secretion of TGF beta from both transformed and nontransformed RPE cells increased if the cells were grown without serum. In conclusion, the results show that TGF beta is expressed and secreted by transformed and nontransformed human RPE cells and that this expression and secretion are regulated by the presence or absence of exogenous factors.