In vivo invasion of human carcinoma of the lung into the cartilage of the bronchus was studied by light microscopy. Tumor spread into the cartilage was found in 26% (60/229). It occurred in 38/128 epidermoid carcinoma (30%) and in 14/55 adenocarcinoma (25%), but was observed in only 1/17 large cell anaplastic carcinoma (6%). Degradation of cartilage matrix was found to be limited. Destroyed area measured 9.9 +/- 1.8 mm2 on average. Tumors able to destroy bronchus cartilage were similar in size compared to tumors without detectable invasion into cartilage. Analysis of pTN stages revealed no differences between both groups. Tumor volume in extrapulmonary lymph nodes was significantly larger in case of cartilage degradation. Patients with tumors degrading bronchus cartilage showed poorer survival (median survival 360 vs. 780 days, p less than 0.10). Immunohistology differentiating inflammatory cells (B lymphocytes, T lymphocytes, monocytes, granulocytes, macrophages) revealed no participation of inflammatory cells in tumorous degradation of cartilage. The findings suggest that hyalin cartilage is highly resistant to invasion of human lung carcinoma although evidence exists for proteolytic activity of human lung carcinoma.