Postprandial chylomicron remnant clearance was studied in six patients with familial combined hyperlipidemia (FCH) and seven control subjects by using an oral retinyl palmitate (RP) fat-loading test. The chylomicron remnant clearance (Sf < 1,000 fraction), expressed as the area under the RP curve (AUC-RP), was delayed in FCH subjects (65.05 +/- 12.84 hours x [mg/L]) compared with control subjects (25.1 +/- 5.4 hours x [mg/L]; p = 0.01). Postprandial lipoprotein particle size and composition in the Sf>> 1,000 fraction were different between FCH and control subjects as analyzed by molecular-sieve chromatography. Fasting high density lipoprotein cholesterol was lower in FCH patients (0.54 +/- 0.09 mmol/L) than in control subjects (0.89 +/- 0.05 mmol/L; p < 0.01). Mean plasma postheparin lipoprotein lipase and hepatic lipase activities were similar between FCH patients (94 +/- 25 and 427 +/- 57 milliunits/mL, respectively) and control subjects (126 +/- 16 and 362 +/- 33 milliunits/mL, respectively). In FCH, a 54% reduction (p < 0.05) of plasma triglycerides to 2.63 +/- 0.41 mmol/L by drug treatment resulted in an enhanced, but not normalized, clearance of chylomicron remnants (39.4 +/- 6.0 hours x [mg/L]). Univariate regression analysis revealed that in FCH subjects the changes in fasting plasma apolipoprotein C-III concentrations after therapy were significantly associated with the changes in chylomicron remnant AUC-RP (r = 0.87; p = 0.02). Delayed elimination of atherogenic chylomicron remnants may contribute to the increased risk of premature atherosclerosis in FCH.