Interferons (IFNs) have been shown to Induce loss of growth potential in melanoma cell lines. However, human melanomas have shown limited responsiveness to clinical therapy with IFN. In a previous study on melanoma cell lines we found that greatest sensitivity to IFN was found in cell lines with the greatest number of copies of chromosome 9p, where the IFN gene family is located. In the present study the expression In melanoma cell lines of IFN genes, IFN receptor genes and standard control genes (beta-actin, glyceraldehyde-3-phosphate dehydrogenase, 18S rRNA and cyclophilin) was investigated using the reverse transcription-polymerase chain reaction, together with an exogenous standard (cyclophllin armoured RNA). We found that the sensitivity to extrinsically supplied IFN seems to correlate with the expression of endogenous IFN genes. The two melanoma cell lines producing the highest relative amount of IFN mRNA transcripts also demonstrated the most marked response to extrinsically supplied IFN. We hypothesize that tumours with enhanced endogenous IFN production may respond more positively to IFN treatment.