Fragments of renal carcinoma of the northern leopard frog, Rana pipiens, were cocultured in vitro with small pieces of tadpole heart, frog heart and frog kidney with gyrotory shaking for up to 14 days at 21 degrees C and 28 degrees C. No invasion by renal carcinoma occurred in confrontation cultures at 21 degrees. However, the three normal tissues were invaded by renal carcinoma in confrontation cultures incubated at 28 degrees C. Invasion in vitro by histologically typical renal carcinoma is thus similar to temperature-dependent invasion by the renal carcinoma-derived cell line PNKT-4B and affords an opportunity for the identification of cell or biochemical events which may be activated at invasion-permissive temperature. Cell or biochemical events which are selectively activated and subsequently repressed as the renal tumor is incubated at invasion-permissive and invasion-restrictive temperatures become significant candidates as events involved in, or causal for, malignant invasion.