Singlet oxygen generated in a dark reaction by thermodissociation of an endoperoxide (NDPO2) elicits an increase in mRNA of interstitial collagenase (MMP-1) in cultured human fibroblasts. The effect is enhanced in deuterium oxide-based medium and is abolished in the presence of non-toxic doses of sodium azide. In contrast, the mRNA level of the tissue inhibitor of metalloproteinases (TIMP-1) remains unaltered under these experimental conditions. These observations support the suggestion that an unbalanced synthesis of collagenase and TIMP reported to occur following UV-A irradiation or during inflammatory conditions may be mediated by singlet oxygen.