Given that we previously reported elevated systemic circulating TNFα levels of 10.45 pg ml−1 in IPAH patients and 9.85 pg ml−1 in HPAH patients compared with 7.92 pg ml−1 in controls12, we suggest that local lung expression is likely to generate appreciably higher TNFα levels and have a more restricted effect on the pulmonary circulation than small elevation in these relatively low systemic levels. The gene discussed is TNF; the disease is idiopathic pulmonary arterial hypertension.