The response of HDL in the acute phase reaction following myocardial infarction (MI) (82 subjects) and acute pancreatitis (AP) (30 subjects) has been examined and compared with that in a control group (76 subjects) admitted to hospital with suspected MI but in whom the diagnosis was not subsequently confirmed. The temporal and quantitative characteristics of the changes in concentration of the positive acute phase reactants fibrinogen and α1-antitrypsin and the negative acute phase reactants albumin and LDL were similar in the myocardial infarction and acute pancreatitis subjects. In contrast, the response of HDL was different to that of the other transport proteins both within each experimental group and between the two groups. This indicated that the response of HDL cannot be regarded as simply part of a secondary negative acute phase reaction. After adjustment for changes in plasma volume, the data indicated that hepatobiliary dysfunction was probably a major factor in the negative response of HDL following acute pancreatitis and may have contributed to its response following myocardial infarction.