Invasion modols of tumor spheroid aggregates in vitro and in vivo were established by using human giant cell carcinoma (lung strain PLA801-95D). PLA801-95D cells from monolayer cultures were suspended and allowed to form spheroid aggregates for 3 d on a gyratory shaker. In organ culture, PLA801-95D (0.2 mm in diameter) were confronted with 0.4 mm round precultured heart fragments (PHF), then co-cultured on a gyratory shaker. PLA801-95D cells showed a strong capacity of invasion in vitro. In vivo, PLA801-95D spheroids (0.3 mm in diameter) were transplanted subcutaneously into the auricles and flanks of BALB/c nude mice. No s. c. tumor growth was noted in the auricle 4 months after transplantation, but at the s. c. flank, tumors were found in 3 of 5 mice, with invasive growth seen at the site of transplantation. Metastases were found in regional drainage lymph nodes (axillary, submaxillary and inguinal lymph nodes) and in the lungs. PLA801-95D cells had high malignancy in vitro and in vivo. Both spheroid invasion models proved to be suitable for judging the malignancy of human tumor cells and for studying the mechanism of human tumor invasion.