The possible growth regulatory role of isoprenoids (mevalonate-derived products) in secondary cultures of normal human mammary epithelial cells (HMEC), as compared to the two human breast cancer cell lines Hs578T and MDA231, was investigated. All three cell types responded promptly to inhibitors of HMG CoA reductase and thereby became arrested. Whereas the growth of MDA231 cells was totally independent of exogenous growth factors, the proliferation of HMEC and Hs578T was blocked or partially blocked, respectively, following growth factor-depletion. Closer analysis showed that the depressive effects on cell growth, induced by HMG CoA reductase inhibition and growth factor depletion, were from a kinetic point of view identical. These data suggest that the biosynthesis of isoprenoids may comprise one event involved in the intracellular mechanisms lying behind the growth factor-mediated growth of mammary epithelial cells. The effects of addition of different known isoprenoids on growth of cells subjected to HMG CoA reductase inhibition or growth factor depletion were also investigated. It was found that coenzyme Q and dolichol significantly delayed growth arrest in all three cell types. In contrast, cholesterol and isopentenyladenine were ineffective.