Addition of aluminum to the culture medium of Nakano mouse lens epithelial (NMLE) cells and Swiss 3T3K cells induced both 3H-thymidine incorporation and mitosis. This is in contrast to other metal ions such as vanadium, which, at concentrations high enough to increase 3H-thymidine incorporation, actually inhibits mitosis (Jones and Reid, J Cell Physiol 121:199, 1984). Aluminum concentrations between 20 microM and 50 microM were most effective. The 3T3 cells respond to aluminum with a 7.6-fold increase, and NMLE cells respond with a 21-fold increase in 3H-thymidine incorporation. DNA synthesis in NMLE cells was also found to be synergistically stimulated by aluminum and low concentrations of insulin (4.5 X 10(-8) M). A 3.25-hr incubation with 50 microM aluminum was sufficient to induce 50% of maximum 3H-thymidine incorporation during the 40-hr assay. Aluminum-stimulated 3H-thymidine incorporation is inhibited by hydroxyurea, and aluminum causes an increase in cell number. Also, by sedimentation equilibrium analysis of the product of aluminum-stimulated DNA synthesis it was found that a single copy of DNA was synthesized following addition of aluminum to quiescent cells. These facts indicate that aluminum induces both S-phase DNA synthesis and mitosis. However, only 48% of the NMLE cells found to be labeled with DNA went on to divide. In contrast, although only a small percentage of 3T3 cells were found to be labeled after aluminum treatment, all of these cells appeared to go through mitosis.