The effects of interferon (IFN) on the expression of the nuclear antigen Ki-67 were studied in the two IFN-sensitive tumour cell lines Daudi and 251 MG, known to be arrested in the cell cycle in separate stages. The GO/G1-arrested Burkitt's lymphoma cell line Daudi displayed an increasing fraction of Ki-67 negative cells with time, concomitant with an increasing proportion of growth arrested cells. A small fraction of Ki-67 positive cells were found mainly arrested in G2/M. In contrast, no effect on Ki-67 expression was seen in IFN-resistant Namalwa cells, nor in the sensitive glioma cell line 251 MG, which is blocked in the S phase of the cell cycle. Agents blocking the cells in other phases of the cycle did not affect Ki-67 expression. However, after serum deprivation, no Ki-67 expression was found in the glioma cell line, while restimulation initiated expression after 12 hours as cells entered the S phase. We conclude that the Ki-67 antigen was not down regulated in all cells inhibited by IFN and thus does not seem to be useful to monitor clinical effects of IFN treatment.