In cardiac transplant recipients, infection with Toxoplasma gondii may be transmitted with the transplanted organ to immunosuppressed recipients or may be due to reactivation under immunosuppression in cases of pretransplant infection. In the present study the incidence of infection with Toxoplasma gondii and the clinical presentation of the infection in 121 consecutive heart transplant recipients were investigated. Data on IgG and IgM antibodies for Toxoplasma gondii measured by a semiquantitative microparticle immunoassay of donors and recipients were collected prospectively in 121 patients. Infection with Toxoplasma gondii was defined as IgM seroconversion with proven pre-transplant seronegativity (primary infection) or at least a fourfold increase of IgG antibodies (reactivation). Infection with Toxoplasma gondii occurred in 16 of 121 patients (13%) whereas overt clinical disease occurred in 5 of 121 patients (4%). Organ-transmitted infection was more frequent (11/18, 61%) and more often associated with acute disease than reactivation of latent infection (5/69 patients, 7%) (p < 0.01), although one case of Toxoplasma retinochoroiditis occurred in a patient with recrudescence of latent pretransplant infection. Treatment with pyrimethamine and sulfadiazine was efficient in all patients with acute disease and in controlling disease in patients with evidence of acute infection.