Borrelia burgdorferi is the causative agent of borreliosis (Lyme disease). This spirochete was first identified in 1995 to cause an infectious arthritis, in the region of Old Lyme, Connecticut. B. burgdorferi produces disease in humans and dogs, with less clearly defined syndromes in cattle, horses and cats. Avian and mammalian wildlife in endemic areas harbor the organism, which is transmitted primarily by ticks of the genus Ixodes. These ticks have 3 hosts during a 2-year life cycle, and the nymph and adult phases may both be sources of infection for dogs. Adult ticks in the northeast commonly feed on white-tailed deer and are frequently referred to as 'deer ticks'.

Other Borrelia spp. have been reported to cause spirochetemia associated with relapsing fevers and hematologic changes that respond to antibiotics, but their prevalence is unknown and no specific diagnostic serologic tests are available.

The prevalence of B. burgdorferi in Ixodes spp. varies regionally. Areas in the United States recognized as endemic include the northeastern and mid-Atlantic states, midwest, and northwest. Of reported cases, 85% are from the northeast, where 50% of ticks in this area may harbor Borrelia spp.

Transmission occurs solely by the tick vector in dogs; other blood-sucking arthropods have not been proven to transmit the disease. There is no direct transmission between dogs, and no vertical transmission has been documented with experimental models that mimic patterns of natural exposure. During prolonged feeding of infected ticks on the host, the organism migrates from the tick's midgut to the salivary gland, and infection occurs. Ticks removed relatively soon (12–24 hours) after attachment are unlikely to cause infection. Dogs are not considered to be a reservoir for human infection, based on the fact that neither the nymph nor adults stages of Ixodes spp. feed alternately on different hosts. Thus, dogs are unlikely to be a source of ticks which will later attach to people. Although spirochete antigen can be found in the urine and saliva of infected dogs, it is labile, virtually impossible to culture, and does not appear to be a source of infection for other dogs or people.

Once an animal has been infected, the spirochetes migrate to target tissues, such as the joints, lymph nodes and connective tissue. The incubation period is long (2–5 months) from the time of infection to the onset of clinical signs.

Serologic studies in dogs from endemic areas suggest that infection with B. burgdorferi most commonly produces asymptomatic seropositive dogs. Seropositive status has been documented for up to 50% of dogs in some areas.

Approximately 5–10% of infected dogs will develop clinical signs. Typically, these dogs are lame, and exhibit varying degrees of joint swelling and myalgia. The lameness typically involves just one leg. Fever, malaise and inappetance can occur but are less common. Untreated, this arthropathy can be self-limiting, but may recur at roughly monthly intervals.

Renal disease, characterized by a membrano-proliferative glomerulonephritis has been associated with Lyme disease. These dogs are azotemic, hypoalbuminemic, and proteinuric. The glomerular lesions are progressive, and the long-term prognosis for these patients is poor. A breed predilection for Labrador and Golden retrievers has been reported.

Heart block and neurologic disease have been reported in association with B. burgdorferi, but are believed to be rare.