The antiproliferative effect of three straight-chained saturated dicarboxylic acids was examined with neonatal mouse keratinocyte cultures. Adipic acid (C6), azelaic acid (C9), and sebacic acid (C10) were added to the cultures in concentrations ranging from 1 to 50 mmol/l. Proliferation was assayed by liquid-scintillation counting of 3H-thymidine incorporation into DNA and by autoradiography. Fifty percent inhibition of 3H-thymidine incorporation was observed with 50 mmol/l adipic acid, 20 mmol/l azelaic acid, and 10 mmol/l sebacic acid, respectively. The antiproliferative effect was completely reversible after cessation of treatment. Moreover, treated cultures then showed a rebound effect with increased DNA synthesis. These results show that dicarboxylic acids exert reversible antiproliferative effects on keratinocytes.