We examined the relationship of human leukocyte antigen (HLA) phenotype to leprosy in six sporadic cases in northern Louisiana and in the world literature through pooling of the results of several studies. We found that HLA antigens DR2 and DQw1 were associated with leprosy in the six cases in northern Louisiana (relative risks, 4.57 for DR2 and 4.53 for DQw1), but the results are not statistically significant. We pooled the Louisiana study and other population studies of HLA and leprosy. The results of the pooling show DR2 and DQwl to be associated with leprosy (relative risks, 2.65 for DR2 and 2.73 for DQw1), and these associations are highly statistically significant (P −8 for DR2 and P = 3.6 × 10−8 for DQw1). Further, we pooled studies of lepromatous leprosy patients vs. controls and studies of tuberculoid leprosy patients vs. controls and found that DR2 and DQw1 are associated with both the lepromatous and the tuberculoid forms of leprosy and that these associations are statistically significant. We consider the associations of DR2 and DQw1 in these population studies to be evidence for an HLA-associated genetic influence on susceptibility to leprosy.