The effects of cytostatic agents on proliferation and epidermal growth factor receptor (EGF-R) expression were examined in the ovarian carcinoma cell line OVCAR-3. These cells were found to express about 84,000 high-affinity EGF binding sites per cell. Treatment of OVCAR-3 cells with cisplatin, etoposide or epirubicin for two hours resulted in a marked augmentation of EGF-R expression and growth inhibition, on the other hand, incubation with substances blocking RNA or protein synthesis, actinomycin-D and cycloheximide, resulted in a reduction of both EGF-R expression and growth rate. An up-regulation of EGF-R has thus been shown only for DNA-affecting agents, but not for those inhibiting transcription or translation. This response may be explained as a frustrated escape mechanism of the cancer cell to cytotoxic agents.