1. To investigate the acute effects of insulin and triacylglycerol ('triglyceride') on circulating plasminogen activator inhibitor-1 concentrations, seven healthy volunteers were studied during hyperinsulinaemic clamps in the presence of euglycemia (mean glucose concentration 5 mmol/l) and hyperglycaemia (mean glucose concentration 9 mmol/l) with and without triacylglycerol infusions. 2. During euglycemia, plasma insulin levels rose from baseline values [median (range)] of 13 (6.6-20.6) m-units/l to 89 (74-105) m-units/l and 99 (74-109) m-units/l after 1 and 2 h of insulin infusion, respectively. Concentrations of plasminogen activator inhibitor-1 fell from 27.5 (10-47) ng/ml to 25.0 (14.5-55) ng/ml and 15.5 (11.5-28.5) ng/ml (P less than 0.02) over the same time. 3. During hyperglycaemia, plasma insulin concentrations were 12.1 (9.3-17.1) m-units/l at the run-in period and rose to 87 (73-112) m-units/l and 91 (84-97) m-units/l after 1 and 2 h of insulin infusion, respectively. Concentrations of plasminogen activator inhibitor-1 again showed a gradual fall from 24.7 (22-50) ng/ml to 14 (8.3-25.5) ng/ml and 13 (6.0-35.0) ng/ml (P less than 0.02) over the same period. 4. Infusion of Intralipid in the presence of hyperinsulinaemia with either euglycemia or hyperglycaemia was associated with a similar fall in concentrations of plasminogen activator inhibitor-1 over the study period. 5. The results from this study indicate that short-term increases in insulin, glucose or triacylglycerol do not cause acute increases in plasma concentrations of plasminogen activator inhibitor-1.