Cocultures of human fibroblasts and LX-1 human lung carcinoma cells expressed 8-10 fold higher levels of collagenase mRNA than the sum of the individual cells, in parallel with similar increases in collagenase activity. Addition of the tumor cell collagenase stimulatory factor, TCSF, purified from LX-1 cells, to these fibroblasts also gave a 3-4 times increase in collagenase mRNA level. However, various fibroblast cell lines differed in their response to TCSF stimulation. Thus one cell line, GM 1391, did not respond to TCSF but responded to another potent collagenase stimulator, tetradecanoyl phorbol ester. Another cell line 5383 did not respond significantly to either agent. In each case collagenase activity and mRNA levels responded in a parallel fashion.