4-Hydroxynonenal, an aldehyde produced from lipid peroxidation of cellular membranes, inhibits growth and induces differentiation of HL-60 human leukemic cell line. Since it is highly unstable in the culture medium, its effectiveness is increased when added repeatedly to the cell suspension. We have previously demonstrated that HNE inhibits c-myc but not N-ras expression in HL-60 cells. Here we investigate its effect on the expression of c-myb and c-fos, two early genes involved in the induction of myeloid and monocytic differentiation. Moreover, since c-fos is directly correlated with the intracellular level of cAMP, we also analysed the cAMP concentration after aldehyde treatment. HNE significantly inhibits c-myb expression during and after repeated treatments. A single administration of 1 microM HNE decreases c-myb mRNA at 1 hour whereas 10 microM HNE inhibits c-myb expression from 3 to 6 hours after treatment, and then the expression returns to the control level. By contrast, c-fos expression and intracellular cAMP concentration do not show any significant change after HNE treatments.