Patterns of cartilage invasion by squamous carcinoma were examined in 40 laryngectomy specimens with particular reference to selective involvement of ossified cartilage. The study determines whether external radiation administered at therapeutic levels to the human larynx has selective effects on the osteoclast cell population and subsequent bone resorption. Radiated and nonirradiated tissues were compared as were cases with and without laryngeal framework involvement by cancer. Morphologic changes in ossified laryngeal cartilage showed that invasion is a largely indirect process dominated by local bone destruction with osteoclasts operating in front of the advancing tumor. Morphometric studies indicate that framework invasion correlates significantly with both increased numbers of osteoclasts and increased bone resorption. An original finding here was that radiation therapy resulted in similarly increased osteoclast activity among cases without framework involvement by cancer. In these cases radiation appeared to act independently of tumor in producing osteoclast activation.