Disturbed Ca2+ handling and altered levels of Ca(2+)-binding proteins (CaBPs) have been found in many transformed cells. To investigate whether there exists a correlation between expression of CaBPs and intracellular Ca2+ we analyzed three transformed rat fibroblast cell lines (T14, T10, and T43) exhibiting different levels of CaBPs. All three cell lines express calmodulin (CaM) at elevated levels compared to normal tissues. In addition, oncomodulin (OM) is expressed at high levels in T14 cells and at much lower levels in T10 cells, while T43 cells do not express OM. We demonstrate that CaBP levels are affected by changes of extracellular [Ca2+] ([Ca2+]o). In reduced [Ca2+]o, CaM levels were increased up to 60%, while OM levels were decreased up to 65% in T14 and T10 cells. Increase of [Ca2+]o, on the other hand, led to a decrease of CaM levels and an increase of OM levels, suggesting that [Ca2+]o exerts its effect on OM and CaM differently. Comparison of the growth rates in reduced [Ca2+]o revealed that T14 cells with the most pronounced CaM increase induced by low [Ca2+]o grew best under these conditions. These results indicate that elevated CaM expression but not the presence of OM reduces the Ca2+ requirement for growth. Intracellular [Ca2+] transients are not buffered by the high concentration of CaBPs in T14 cells. In contrast, [Ca2+]i transients induced by increase of [Ca2+]o or addition of serum were most pronounced in T14 cells compared to T10 and T43 cells.