The ability of culture dishes coated with an extracellular matrix (ECM) to act as a suitable substrate for human ovarian carcinoma cells in vitro has been examined. The plating efficiency on ECM was 30 to 80% (dispersed tumor cells from solid tumor tissue and effusions) with active proliferation of tumor cells being observed. Within a few min, ovarian carcinoma cells seeded on an ECM were noted to attach firmly and assume a flattened morphology. In addition, ovarian carcinoma cells maintained on ECM-coated dishes could be released easily via trypsinization or with a cell scraper. This is in marked contradistinction to tumor cells seeded onto plastic dishes without an ECM. Invasion through the ECM by tumor cells from solid tumor tissue was occasionally noted. Nonmalignant cells were removed from dispersed tumor cell preparations by preplating on plastic culture dishes without an ECM. The malignant origin of the tumor cells was confirmed by morphological, histochemical, and cytogenetic criteria. This culture system represents a significant improvement over current methods for routinely culturing human ovarian carcinoma cells. Such a model may be utilized for screening anticancer drugs for their ability to inhibit proliferation of human ovarian carcinoma cells from individual patients. This system also may be useful for elucidating mechanisms of ovarian tumor cell attachment and invasion in the process of metastasis.