OBJECTIVE In order to assess the consequences of different clinical approaches in the prenatal management of congenital toxoplasmosis, we retrospectively reviewed 58 pregnant women with Toxoplasma seroconversion and prospectively enrolled their 59 infants, referred to us from 1999 to 2004. METHODS Data on clinical, laboratory and demographic characteristics of the pregnant women were collected. Their children were entered into a 48-month follow-up programme in which clinical, instrumental, ophthalmologic and serologic evaluations were carried out at birth, at 1, 3, 6, 9, 15, 18, 24, 36 and at 48 months of life. Paediatric treatment with Spiramycin alone or alternated with Pyrimethamine-Sulphadiazine was administered according to the different clinical cases. RESULTS Time of infection was dated in the first trimester for 24 women (41%), in the second trimester for 18 women (31%) and in the third trimester for 16 (28%). In the first trimester of pregnancy 20 of the 24 infected women had undergone amniocentesis, while the test had not been performed on any of the women infected in the third trimester. Serological follow-up revealed that 11 (19%) of the infants had been infected. An alternating regimen with Pyrimethamine-Sulphadoxine was administered to the infected children. All the infants were clinically asymptomatic, and the instrumental follow-up revealed specific toxoplasmosis anomalies in 4/11 infected children. CONCLUSIONS Our results highlight issues and problems concerning current prenatal diagnostic tests and the therapeutic approach based on PCR testing of amniotic fluid alone. The incidence of ocular-cerebral lesions observed in children born to women with seroconversion in the third trimester raises questions about the diagnostic and therapeutic approach for these women and their offspring. Paediatric therapeutic protocol, with alternating Pyrimethamine-Sulphadiazine regimen, applied also to asymptomatic children born to women with inadequate prenatal diagnostic management, could prevent severe sequelae.