All examined isolates of the Lyme disease spirochete contain multiple operons encoding Erp outer membrane lipoproteins. Many Erp proteins have been demonstrated to bind the host complement regulator factor H, and may thereby help protect the bacteria from complement-mediated killing during mammalian infection. Consistent with that hypothesis, all Erp proteins are produced by Borrelia burgdorferi during transmission between tick vectors and mammalian hosts. The present study examined whether erp genes are also expressed by B. burgdorferi following establishment of mammalian infection. To that end, quantitative RT-PCR was utilized to assess erp transcription levels within different tissues of infected non-human primates, a model that closely mimics human Lyme disease. The majority of erp genes were detectably transcribed after more than 3 months of mammalian infection. Intriguingly, differences in expression levels were noted among the various erp loci. No significant differences in erp expression were apparent between examined tissues, which included central and peripheral nervous system tissue, skeletal muscle, bladder, skin and heart tissues. These data strongly suggest that Erp proteins are expressed by B. burgdorferi throughout infection of their vertebrate hosts.