Plasma lipid concentrations are known to vary on an intraindividual basis. Yet the possible significance of such variability in important predictors of coronary heart disease (CHD) remains as obscure as the aetiology. We examined for association between intraindividual medium term variations in plasma total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride concentrations and genetic identity (TG) at the APOA2 and HL loci.Variability was assessed as the root mean square error (RMSE) of a chronological regression of 5 samples taken over a 13 week period from 42 unrelated subjects with primary hypercholesterolaemia (TC > 6.5 mmol/l). Genotypes were established by endonuclease restriction of two biallelic polymorphorisms using polymerase amplified gDNA (APOA2) 3 untranscribed MspI; HL exon 5 Msp I).TC RMSE was differential according to APOA2 genotypes (p < 0.05 kw) with LDL-C RMSE'S showing similar trends (p < .10). HDL-C RMSE's were differential by HL genotype (< 0.005) with TG RMSE showing a consistent trend (p < 0.10). We suggest that variations at these loci may help determine the intraindividual variability of TC and HDL-C. The significance of such variability remains to be established, though long-term TC RMSE was an independent predictor of CHD risk in the Framingham study.