An Ets-related E1A-F has been characterized as an enhancer-binding protein for the adenovirus E1A gene. Here we show, in transient expression assays, that E1A-F can activate three different subclasses of the matrix metalloproteinase gene promoters. Expressions of the chloramphenicol acetyltransferase (CAT) reporter gene under the control of stromelysin, type I collagenase and 92 kD type IV collagenase promoters were increased approximately 10- to 20-fold by co-transfection with the E1A-F expression vector. Activation levels were as much high as those obtained by exogenous expression of AP-1 transcription factor. These results suggest that E1A-F positively regulates transcriptions from matrix metalloproteinase genes that are associated with invasion and metastasis of tumor cells.