Pre-treatment of metastatic human lung cancer cell subline (PGCL3) with all trans retinoic acid (RA) resulted in inhibition of cell growth in vitro and invasion through the reconstituted basement membrane. RA was also noticed to inhibit the experimental metastatic ability of PGCL3. Data showed that 5/6, 3/6 and 2/6 of the nude mice developed lung colonization in the control, the 5 mumol/L and the 10 mumol/L RA treated PGCL3 cells respectively. Data from DNA-RNA dot blot hybridization further showed that the 10 mumol/L RA treated cells expressed high levels of the human tissue inhibitors of metalloproteinases (Timp-1 and Timp-2) in comparing to the untreated cells. These results may help to clarify the mechanism of RA-induced inhibition effect on tumor invasion and metastasis.