Objective: We have previously observed low levels of high density lipoprotein (HDL) cholesterol in active sarcoidosis. The aim of this study was to analyze the role of serum amyloid A (SAA) on this lipid disorder. Methods: Eighty five untreated sarcoid patients, 40 with active disease and 45 with inactive disease, were recruited. Sarcoidosis activity was evaluated by means of clinical, chest X-ray, gallium-67 scan, serum angiotensin converting enzyme (peptidyl-dipeptidase A) values, and pulmonary function tests. Analysis of lipoprotein metabolism included: serum cholesterol, low density lipoprotein (LDL)-cholesterol, HDL-cholesterol, HDL,-cholesterol, HDL,-cholesterol, apolipoprotein A-I (apo A-I), apolipoprotein B (apo B), and triglyceride concentrations. Serum amyloid A protein and lecithin-cholesterol acyltransferase (LCAT) activity were measured. Results: In active sarcoidosis we found significantly reduced levels of HDL-cholesterol (1.17 +/- 0.36 vs. 1.44 +/- 0.39 mmol/l, P = 0.002), HDL3-cholesterol (0.78 +/- 0.23 vs. 1.02 +/- 0.21 mmol/l, P < 0.0001), and apo A-I (1.36 +/- 0.29 vs. 1.61 +/- 0.27 g/l, P < 0.0001) and significantly increased levels of triglyceride (1.51 +/- 0.64 vs. 1.03 +/- 0.46 mmol/l, P < 0.0001), and apo B (1.14 +/- 0.25 vs. 0.99 +/- 0.27 g/l, P = 0.012) versus inactive sarcoidosis. Serum amyloid A concentrations were significantly increased in the patients with active disease (155.45 +/- 154.01 mg/ml) compared to the inactive sarcoid patients (89.70 +/- 65.36 mg/ml) (P = 0.011). There were no significant differences in cholesterol, LDL-cholesterol, HDL,-cholesterol or LCAT values between groups. Multivariate logistic regression analysis showed that HDL-cholestrrol (regression coefficient b = - 1.96; S.E. = 0.87; P = 0.02) and SAA (regression coefficient b = 0.01; S.E. = 0.004; P = 0.01) were the two variables independently associated with disease activity. Moreover, a significant negative correlation was observed between SAA levels and both HDL-cholesterol (r = - 0.39; P = 0.01) and apo A-I (r = - 0.35; P = 0.03) levels, in the active sarcoid group. Conversely, no correlation was found in the inactive sarcoid group. Conclusion: The low HDL-cholesterol and apo A-I concentrations seen in active sarcoid patients are associated with a significant increase of SAA levels. We suggest that the displacement of apo A-I by SAA on HDL accounts for the lower level of HDL-cholesterol seen in active sarcoidosis. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.