Regression of feline immunodeficiency virus (FIV) infection was observed in seven of nine vertically infected kittens born to two chronically infected mother cats. Both provirus and nonmaternal FIV antibody were detected in all kittens by 4 weeks of age but only three of the seven kittens were positive by blood mononuclear cell coculture. Between 10 and 14 months of age blood mononuclear cells from each of the seven cats were negative at least once by polymerase chain reaction (PCR), but evidence of virus infection was detected by coculture and/or PCR in biopsied lymph node or bone marrow from five of the seven cats. Despite this evidence of persistent tissue provirus, antibody production did not persist in any of the cats beyond 1 year of age. All seven cats remained asymptomatic although CD4 and CD8 T cell counts were in the low normal range throughout the study. By contrast, two additional perinatally infected littermates that were persistently virus isolation positive developed rapid CD4 depletion and progressed to terminal immunodeficiency by 9 weeks of age. Thus FIV infection can be downregulated and/or sequestered to extremely low levels barely detectable with the assays available, although absolute clearance of virus may not occur. These observations are relevant to human immunodeficiency virus (HIV) infection in paralleling both the apparent "regression" of HIV infection reported in some perinatally infected infants and the low-level, apparently stable, infection established by attenuated simian immunodeficiency viruses.