Small cell carcinoma of the lung is frequently associated with a paraneoplastic syndrome or constitutional symptoms. To examine correlations between paraneoplastic syndromes or constitutional symptoms and tumor behavior, the clinical and pathologic features were reviewed in 85 patients with small cell carcinoma of the lung who underwent complete autopsy at The Johns Hopkins Hospital between 1962 and 1983. The 28 (33 percent) subjects with a paraneoplastic syndrome survived significantly longer (10.5 +/- 1.5 months) than those without a paraneoplastic syndrome (7.4 +/- 0.7 months) (p less than 0.05), and they had significantly higher frequencies of tumor invasion into major bronchi (p less than 0.01) and more extensive metastases to bone marrow (p less than 0.05), but significantly lower frequencies of and less extensive metastases to the central nervous system (p less than 0.005). The 35 (41 percent) subjects with constitutional symptoms had markedly increased tumor burdens (p less than 0.005) with significantly more extensive metastases to bone marrow, liver, and lungs (all p less than 0.05). The findings suggest that subjects with small cell carcinoma of the lung associated with a paraneoplastic syndrome tend to have a more benign clinical course with prolonged survival; in addition, the significantly lower frequency of central nervous system metastases in these patients may be due to a paucity of the subpopulations of tumor cells that have the propensity to metastasize to the brain. In contrast, it appears that constitutional symptoms develop in patients with small cell carcinoma of the lung because of rapid tumor growth, coupled with impairment of synthetic activity in the liver due to extensive infiltration of tumor into hepatic parenchyma.