The true prevalence of pulmonary lymphangioleiomyomatosis (LAM) in patients with tuberous sclerosis complex (TSC) is unknown. The prevalence of LAM, radiological features, and lung function in patients with TSC was measured. The presence of LAM, as defined by the presence of cysts by high-resolution chest computed tomography (HRCT) scan, was determined in patients with TSC without prior pulmonary disease (Group 1). To determine the significance of early detection, severity of disease in screened patients (Group 1) was compared with that in patients with TSC with a prior diagnosis of LAM (Group 2). Forty-eight patients with TSC and no prior history of LAM were screened. Of the 38 females, 13 (34%) had LAM; LAM was absent in males. Lung function was preserved in patients with TSC who were found to have LAM by screening. In patients previously known to have LAM, FEV(1) and DL(CO) correlated inversely with severity of disease as assessed by CT scan. The prevalence of LAM in women with TSC was 34%, approximately 10-fold that previously reported, consistent with a large hitherto unrecognized subclinical population of patients at risk for pulmonary complications.