We have compared the effect of interleukin-4 and transforming growth factor beta 1 on proliferation and gene expression in two colorectal carcinoma cell lines, LS513 and LS1034. Transforming growth factor beta 1 was a potent inhibitor for both cells lines and virtually abolished de novo DNA synthesis. Interleukin-4 inhibited thymidine incorporation up to 60 and 45%, respectively. While both cytokines exerted a comparable cyto-inhibitory activity they displayed differential effects on proto-oncogene expression. Transforming growth factor beta 1 markedly down-regulated c-myc in LS1034 but not in LS513 cells. In contrast, expression of c-fos was induced by interleukin-4 in LS513 but not in LS1034 cells. Interestingly, in agreement with their cyto-inhibitory activity both cytokines suppressed the expression of insulin-like growth factor II in LS1034, which is an autocrine growth factor for these cells.