We have examined 60 colorectal carcinomas for activation of two proto-oncogenes, c-myc and c-Ki-ras. Over-expression of c-myc mRNA as determined by Northern analysis was found in 58% of cases (35/60). Activation of the c-Ki-ras gene by point mutations in codons 12 or 13 as determined by mismatch specific oligonucleotide hybridisation was found in 35% (21/60) of cases. There was a statistically significant association between activation of c-Ki-ras and over-expression of c-myc (P = 0.03), with 76% of tumours with an activated c-Ki-ras proto-oncogene showing over-expression of c-myc. The association was significant in left-sided colorectal tumours (P = 0.03) but not right-sided (P = 0.5). However, whereas only 59% of left side tumours showed at least one of the two changes (ras activation only, or myc activation only or both), 93% of right side tumours showed at least one of the changes (P = 0.01). Twenty-two percent of left side tumours showed both changes compared with 35% of right side tumours, although this result did not achieve significance (P = 0.2). These results suggest that in left-sided colorectal tumours ras and myc cooperate, as established in vitro, to produce neoplastic transformation while different pathway(s) are involved in right-sided tumours.