There is increasing evidence that the cells of the epithelial root sheath synthesize enamel matrix proteins and that these proteins play a fundamental role in cementogenesis and periodontal tissue formation. Emdogain, enamel matrix derivative (EMD), is a porcine enamel matrix derived product used to enhance regeneration of the peridontium after inflammatory destruction. Today, little is known about EMD's potential regenerative properties on cell function. The purpose of this study was to investigate the effects of EMD on mouse fibroblasts (L 929 cells) and rat marrow stromal osteoblasts. For effects on cell proliferation, the L 929 cell lines were plated in 24-well culture plates at an initial density of 10,000 cell/mL and allowed to attach. Following a 24-h incubation within Dulbecco's modified eagle medium (DMEM) enriched with 10% fetal bovine serum, DMEM supplemented with 0 (Control), 50 mug/mL and 100 mug/mL of EMD was added and cultures maintained for 96h. Cell proliferation was measured at 24, 48, 72 and 96 h as the total cell number per well and cell morphology was investigated. Osteoblasts were digested from mouse tibia marrow and were plated in similar manner as with L 929 cells, while the observation periods were 2, 6, 8 and 10 days in this group. Although both cell types were able to maintain their original cell morphology throughout the tests, in both cell groups the number of cells in the EMD groups at each observation period were not significantly different than that in the control group (ANOVA, P > 0.05). Moreover, EMD failed to show any impact on cell growth with higher concentration (ANOVA, P > 0.05). These results suggest that although EMD had no cytotoxic effect on mouse fibroblasts and stromal marrow osteoblasts, the same material failed to enhance the growth of both cell types.