Non-steroidal anti-inflammatory drugs (NSAIDs) reduce the incidence of colorectal carcinoma. We now report that the potent cyclooxygenase-1 inhibitor indomethacin had no effect on the growth of human colorectal carcinoma cell lines in vitro at concentrations up to 30 microM. The selective cyclooxygenase-2 inhibitors L-745337 and NS-398 reduced cyclooxygenase activity, but had no effect on cell growth at concentrations as high as 100 microM. Our results provide direct evidence that inhibition of cyclooxygenase activity does not necessarily inhibit the growth of colorectal carcinoma cell lines and imply that the growth-inhibitory effects of NSAIDs in vitro are not mediated by inhibition of cyclooxygenases.