We studied the inhibitory effect of γ-interferon on the expression of LDH A gene at the transcriptional level during regeneration of rat liver. Also, we examined the possible involvement of cAMP as a second messenger for the inhibition of LDH A gene expression and DNA synthesis by γ-interferon after partial hepatectomy of rat. γ-Interferon (1×10⁴IU/100g of rat. i.p.) injected at 20 h prior to partial hepatectomy reduced LDH A mRNA concentration at 21 h and inhibited DNA synthesis at 24 h after the partial hepatectomy. Dibutyryl cAMP (0.5 ㎎/100 g of rat, i.p.) injected at 8-12 h after partial hepatectomy restored both the LDH A mRNA concentration and the DNA synthetic activities which were inhibited by γ-interferon. However, γ-interferon did not affect the cAMP levels determined by RIA method in regenerating rat liver. The above results suggest that during regeneration of rat liver, the inhibitory effects of γ-interferon on the induction of LDH A gene transcription and the DNA synthesis, both of which activities were reported to be regulated by cAMP, may not be mediated by cAMP, but may be mediated by the inhibition of c-myc protooncogene expression.