To study the relationship between cell growth and differentiation in human keratinocytes, we examined the effect of the antisense oligomer of c-myc mRNA. This oligomer is stable in culture medium. A 24 h incubation of cells with 5 microM antisense c-myc oligomer resulted in a 48.2% decrease in c-myc protein and inhibited cell growth by 80.7% compared to the sense c-myc oligomer. In contrast, antisense c-myc oligomer had no effect on differentiation when the population of involucrin-positive cells and cornified envelope formation were used as differentiation markers. These results show that antisense c-myc oligomer inhibits cell growth but does not induce differentiation in normal human keratinocytes. Therefore, cell growth and differentiation are not necessarily coupled in these cells.