AbstractCells derived from human germ cell tumors (HGCT) are potential models for the study of human embryonic differentiation. Differentiation in four HGCT-derived lines (1618K, 833KE, 1777Ndif, 2806B) was examined by light and electron microscopy, after exposure of cells to dimethyl sulfoxide (DMSO) and 12-0-tetradecanoyl phorbol-13-acetate (TPA). In line 1618K, the effect of retinoic acid was also examined. After exposure to TPA, the cells of line 1618K had a loss of microvilli, an increased amount of nuclear heterochromatin, and an increase in the number of cytoplasmic vacuoles. The cells of line 833KE exposed to TPA showed only an increase in cytoplasmic vacuoles. No changes were observed in any cell line after exposure to DMSO. Similarly no changes were observed in 1618K after exposure to retinoic acid. These findings indicate that DMSO and retinoic acid are not effective inducers of differentiation in these HGCT-derived cell lines. Thephorbol ester, TPA, appears to induce differentiation of some HGCT-derived cell lines.