The cytokinetics and growth effects of retinnic acid (RA) (13-cis-RA, and all-trans-RA) were determined in human embryonic palatal mesenchymal (HEPM) cells using cell culture and sister chromatid differential staining. The lowest concentration tested that showed growth inhibition was 1.0×10-4 M for 13-cis-RA, and 6.8×10-5 M for all-trans-RA after 40 h of treatment. When HEPM cells were grown in the presence of BrdU (5-bromodeoxyuridine) for 44 h, approximately 70% of the control cells were in metaphase in the 3rd replication cycle (M3). The percentage of cells in M3 decreased in the presence of RA with or without a metabolic activation system (S-9), thus indicating a longer cell proliferation time for the RA-treated cells. The estimate of cell proliferation time in 13-cis-RA-treated cells (1.0×10-4 M) was approximately 25 h at the 2nd cell cycle compared with 20 h in the control cells. When HEPM cells were exposed for 16 h to [3H] -thymidine, labeling indices in 13-cis-RA-treated cells were significantly reduced even at 1.0×10-6 M. Both 13-cis-RA and all-trans-RA caused concentration-dependent decreases in [3H] -thymidine incorporation into HEPM cells. These results suggest that retinoic acids or their major metabolites interfere with DNA synthesis and decrease the proliferation of HEPM cells.