OBJECTIVES: To evaluate whether fetal serum beta2-microglobulin could be used as a marker of fetal cytomegalovirus (CMV) or toxoplasmosis infection. METHODS: beta2-microglobulin was retrospectively assayed in fetal serum collected from 64 patients with maternal infectious seroconversion (toxoplasmosis in 49 cases, CMV in 15). Using a beta2-microglobulin cutoff of 5 mg/L, infection and control groups were compared. RESULTS: Fetal serum beta2-microglobulin was >5 mg/L (5.2-13.5 mg/L) in 12 of the 13 cases with proved fetal toxoplasmosis infection, indicating 90% sensitivity. In the 39 pregnancies with maternal seroconversion but no laboratory signs of fetal infection, fetal serum beta2-microglobulin was <5 mg/L, indicating 100% specificity. Fetal serum was >5 mg/L (6.3-32 mg/L) in 14 of the 15 cases with proved fetal CMV infection, indicating 93.3% sensitivity. Specificity cannot be evaluated because maternal serum is not routinely screened for CMV during pregnancy. CONCLUSIONS: Fetal serum beta2-microglobulin is a reliable marker of fetal CMV or toxoplasmosis infection, which can be used in ambiguous situations. Because this increase is not specific, fetal serum beta2-microglobulin would potentially be raised in other fetal infections.