The expression of insulin-like growth factor-II (IGF-II) in normal human first and third trimester placental tissue was investigated by non-isotopic in situ hybridization (ISH). This is the first ISH study on IGF-II expression in placenta using an alkaline phosphatase-labelled probe. The expression was correlated with the proliferative activity of the cells using the proliferative marker MIB-1. In first trimester tissue, IGF-II was expressed in the cytotrophoblast, the extravillous trophoblast, the fetal endothelial cells and the mesenchymal fetal cells in the villi. In third trimester tissue, IGF-II expression was found in the amnion, the extravillous trophoblast and the mesenchymal fetal cells especially in the endothelial cells and the outer contractile sheet in the stem villi. In areas with perivillous fibrin deposits, strong expression of IGF-II was found in the cytotrophoblasts invading the fibrin. In first trimester tissue, the proliferative activity of the villous cytotrophoblast correlated well with the degree of IGF-II expression whereas in third trimester tissue, there was a discrepancy between MIB-1 positivity and the IGF-II expression. Expression of IGF-II does not seem to be correlated exclusively to the mitogenic activity of cells.