Abstract The inhibitory action of methyl glyoxal upon protein, RNA and DNA synthesis in guinea pig keratocytes has been investigated. Methyl glyoxal directly inhibits each of these processes. Inhibition of protein synthesis results from an action upon initiation of translation. Methyl glyoxal induces polysome degradation which is prevented by pretreatment with cycloheximide. Further analysis of translation indicates that elongation and termination are not affected. Inhibition of ribosomal RNA synthesis results from inhibition of maturation. Methyl glyoxal was found to inhibit the appearance of 28S rRNA in the cytoplasm from pulse-labelled precursors. The significance of these results is discussed in relation to cell injury by ketals.