Lysosomal acid lipase (LAL) is a key enzyme involved in intracellular hydrolysis of cholesteryl esters and triglycerides. Here we report a novel restriction fragment length polymorphism (RFLP) of Thrl6Pro (A^(+46) →C) in human LAL gene exon 2. The mutation was genotyped by the PCR and subsequent digestion using HaeIII. We examined the genotype distributions in subjects with Korean normal (n=198) and hypercholesterolaemia groups (n=81). The observed AA, AC and CC genotype numbers in control group were 95, 88 and 15, respectively (frequency of A=0.702, C= 0.298). The genotype numbers in disease group were 28, 41 and l2, respectively (A=0.599, C=0.401). Each group showed some frequency differences, but it was no significantly different. However, significant differences were found in genotype distributions between control and disease groups (χ²=6.28, df=2, 0.025