The high triglyceride/low HDL-cholesterol trait is a common finding in the general population. The aim of the present study was to analyze and interpret the relationships between triglycerides (TG), HDL-related parameters and serum cholesterol efflux potential in an asymptomatic population including both normo- and hyperlipidemic individuals. In a large sample (n = 1143) of this population, there was a negative correlation between TG and HDL-cholesterol (HDL-C) (r = -0.49, P<0.0001) whereas the negative correlation between TG and HDL-phospholipid (HDL-PL) (r = -0.29, P<0.0001) was weaker, leading to a strong positive correlation between TG and HDL-PL/C ratio (r = 0.58, P<0.0001). Thus, increased TG concentrations were associated with an enrichment of HDL with PL. Since we have demonstrated previously that HDL-PL is the major determinant for cholesterol efflux potential from Fu5AH rat hepatoma cells, we determined the effect of the variations in HDL lipid composition on the cholesterol efflux capacity in a subsample of 198 subjects. Compared with normolipidemic subjects (NLP) (TG< or = 1.7 mmol/l; LDL-C< or = 4.1 mmol/l, n=58), hypertriglyceridemic subjects (HTG) (TG>1.7 mmol/l, n=63) exhibited lower HDL-C levels (1.08+/-0.21 vs. 1.25+/-0.32, P=0.0003) whereas they showed similar HDL-PL concentrations (1.25+/-0.21 vs. 1.25+/-2.7) and, thus, higher HDL-PL/C ratio (1.17+/-0.15 vs. 1.02+/-0.14, P=0.0001). The relative efflux capacity of serum measured in the Fu5AH system (5% serum, 4 h incubation at 37 degrees C) was on average identical in the HTG and NLP groups. Thus, this study provides evidence that despite decreased HDL concentrations, as determined routinely by the HDL-C assay, some HTG subjects maintained serum cholesterol efflux capacity thanks to the enrichment of HDL with PL.