Pulmonary lymphangioleiomyomatosis (LAM) is a rare interstitial disorder affecting exclusively women, and leading to progressive deterioration of lung function. The disease course is highly variable from one patient to another, but no clinical predictor of rapid disease progression is currently available. To identify clinical variables, which could detect patients at risk for rapid lung function decline, we searched for correlations between the rate of forced expiratory volume in 1s (FEV₁) decline and clinical features at diagnosis in a retrospective series of 31 cases of LAM followed for ⩾1yr. The mean FEV₁ decline was 106±143ml/yr or 3.4±4.6% predicted FEV₁/yr. Among clinical features at diagnosis, only initial values of carbon monoxide transfer factor (TLCO, P=0.006) and carbon monoxide transfer coefficient (KCO, P=0.0001) were significantly correlated with the rate of FEV₁ decline. Lung volumes and FEV₁/forced vital capacity ratio at diagnosis were not predictive of rapid decline. No effect of previous smoking, contraceptive use or pregnancy on FEV₁ decline could be detected. We conclude that low TLCO and KCO at the time of diagnosis are the best clinical predictors of rapid FEV₁ decline in patients with LAM.