A distinctive renal lesion consisting of glomerulonephritis, diffuse tubular necrosis with regeneration, and interstitial inflammation was found in 49 biopsy/necropsy cases obtained from 1987 to 1992. This lesion is manifested clinically as a rapidly progressive glomerular disease that was uniformly fatal. Immune-mediated membranoproliferative glomerulonephritis predominated (43/49, 88%). Membranous glomerulonephritis (5/49, 10%) and amyloidosis (1/49, 2%) were also noted. Subendothelial deposits, IgG, IgM, and C3 were present along glomerular basement membranes. IgA was absent. The exact cause of the tubular necrosis is unknown. Affected dogs were significantly younger (5.6 +/- 2.6 years) than dogs with other forms of glomerulonephritis (7.1 +/- 3.6 years) and amyloidosis (7.8 +/- 3.5 years) both in the studied population for the same period and in the reported canine population. Labrador and Golden retrievers were 6.4 and 4.9 times more likely, respectively, to develop this lesion. This is the first report of a breed predilection for spontaneous canine glomerulonephritis. Previous reports have associated this lesion with Borrelia burgdorferi exposure. All dogs in this study were from Lyme disease-endemic areas. Of 18 dogs serologically tested, all were positive for exposure. Silver stain examination of kidneys revealed rare spirochetes, suggesting that the presence of spirochetes in the kidney is apparently unrelated to lesion development. The role of vaccination in development of the renal lesion is undetermined. The association of this histologically and clinically unique lesion, Lyme nephritis, with Borrelia burgdorferi infection is significant because it is the only fatal form of canine Lyme borreliosis.