<i>Objective:</i> Analyze the information contained in homozygous haplotypes detected with high density genotyping. <i>Methods:</i> We analyze the genotypes of ∼2,500 markers on chr 22 in 12 population samples, each including 200 individuals. We develop a measure of disequilibrium based on haplotype homozygosity and an algorithm to identify genomic segments characterized by non-random homozygosity (NRH), taking into account allele frequencies, missing data, genotyping error, and linkage disequilibrium. <i>Results:</i> We show how our measure of linkage disequilibrium based on homozygosity leads to results comparable to those of <i>R</i>², as well as the importance of correcting for small sample variation when evaluating <i>D</i>′. We observe that the regions that harbor NRH segments tend to be consistent across populations, are gene rich, and are characterized by lower recombination. <i>Conclusions:</i> It is crucial to take into account LD patterns when interpreting long stretches of homozygous markers.