Purpose: Apoptosis inhibition may be a strategy by which mutated cells evade normal clearance mechanisms and lead to development of colorectal cancer (CRC). We determined the expression of the apoptosis inhibitor bcl-2 in normal colon mucosa and 21 CRC metastases by RT-PCR analysis and correlated it to p53 and c-myc expression in the same samples.Methods: Material from 21 liver CRC metastases was obtained at surgery, and total RNA was extracted and reverse transcribed into c-DNA. The target genes bcl-2, p53 and c-myc were amplified together with b-actin and b-2Microglobulin using published primers in differential PCR reactions, and the ratios between target genes in metastases and normal colon mucosa were determined.Results: Compared to normal mucosa controls (= 1U), the relative bcl-2 mRNA expression was lower in CRC metastases (mean 0.45 U, p < 0.0001. p53 expression was reciprocal to bcl-2 expression (p = 0.021) in 19 evaluable samples. In tumours overexpressing p53 (more than two-fold elevated over normal controls), bcl-2 mRNA was significantly decreased (p = 0.0052). c-myc was also inversely correlated with bcl-2 expression (p = 0.025).Conclusion: bcl-2 mRNA expression is reduced in CRC metastases compared to normal mucosa. bcl-2 is reciprocally expressed to p53 and c-myc, two genes also involved in apoptosis and altered late during colorectal tumourigenesis. This inverse correlation suggests an active down-regulation of bcl-2 following possible delegation of its apoptosis inhibiting function to other genes.