We report on clinical and metabolic studies of a newly delineated lipomatosis, characterised by an abnormal mediastinal and abdominal accumulation of fat, without obesity. The clinical features, which occurred in all the patients studied, are: Exertional dyspnoea due to a space-occupying mediastinal accumulation of fat, without evidence of cardiac or pulmonary disease. A pseudo-ascitic abdominal enlargement, due to intra- and retroperitoneal accumulation of fatty tissue. Insulin-independent diabetes mellitus. Type IV hyperlipidaemia and elevated levels of plasma uric acid were observed in four patients. Intra-abdominal lipomatous tissue, obtained during laparoscopy from four patients, demonstrated a reduced lipolytic response to beta-adrenergic stimulation. Thus, fat deposition in the abdominal and mediastinal areas could be causally related to defective lipid mobilization in lipomatocytes. Lipoprotein lipase activity in abdominal adipose tissue were normal in two patients (10.0 and 10.6 nmol/g/min) and markedly elevated in another two patients (37.3 and 49.9 nmol/g/min), as compared with controls (12.7 +/- 2.1 nmol/g/min). When expressed on per cell basis, LPL activity in lipomatous tissue was significantly higher than in control tissue (3.21 +/- 1.1 nmol/10(5) cell/min vs 0.92 +/- 0.16 nmol/10(5) cell/min). Lipoprotein fractionation did not demonstrate consistent modification of the serum lipoprotein pattern. HDL and HDL2 cholesterol values were reduced, even in patients with elevated LPL activity in adipose tissue.