We have shown previously that a hepatic lipase allele (designated -514T) is common among African Americans and contributes to low hepatic lipase activity in this population. To identify other hepatic lipase alleles associated with low hepatic lipase activity in this population, the coding region and intron-exon boundaries of the hepatic lipase gene were sequenced in 20 African American men with low hepatic lipase activity. Two polymorphisms (N193S and L334F) were associated with low post-heparin plasma hepatic lipase activity and were much more common in African Americans than in whites. This finding, together with our previous data on the -514T allele, indicates that at least three different hepatic lipase polymorphisms associated with low hepatic lipase activity are common among African Americans. Analysis of hepatic lipase haplotypes revealed that 97% of African Americans have at least one hepatic lipase allele that is associated with low hepatic lipase activity.