The insulin-like growth factor-1 receptor (IGF-1R) and its possible protective effect on apoptotic cell death in malignant melanoma was analysed in four commercial melanoma cell lines. Inhibition of N-linked glycosylation by tunicamycin, which has previously been shown to block the translocation of IGF-1R to the cell surface, blocked cell growth and/or induced cell death in these cell lines. Treatment with alphaIR-3, an antibody blocking the binding domain of IGF-1R, also resulted in growth arrest and/or apoptosis. We also analysed lymph node metastases of malignant melanoma by Western blotting and immunohistochemistry. All these cases were shown to express IGF-1R at the cell surface. In three cases of lymph node metastases we had access to both tumour specimens and cultured cells. One of these exhibited a substantially higher expression of IGF-1R than the two other cases. The corresponding cell lines showed growth arrest and apoptosis following treatment with alphaIR-3. However, the two cell lines with low expression of IGF-1R were more sensitive in this respect. Furthermore, we demonstrated an inverse correlation between IGF-1R expression and the frequency of apoptotic cells in the tumour specimens. Our data suggest that IGF-1R is crucial for the viability of malignant melanoma cells in vitro as well as in vivo.