Patients with congenital toxoplasmosis occasionally show rises in serum antibodies to Toxoplasma gondii (serological rebound), but the underlying cause remains unclear. The acute or chronic presence of available antigen often causes the appearance, in the peripheral blood, of cells actively secreting specific antibody. We have evaluated the capacity of circulating blood cells from 91 children born to T. gondii-infected mothers to actively synthesize anti-T. gondii antibodies according to their serological status. Supernatants from 7-day cultures of peripheral blood mononuclear cells were evaluated for antibody by cytofluorimetry. Only 1 of 49 subjects with low and stable serum antibody titers produced specific antibodies on cultures, while 9 of 22 subjects with recent rebound were positive. One of the positive children alone showed clinical signs of parasite activity. These observations suggest that rebound may be associated with production of available parasite antigens, possibly associated with reactivation. Differentiation from other causes, such as polyclonal B cell stimulation, would improve our ability to detect clinically significant reactivation and to prevent complications.