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Background: The development of suppressive therapy and type specific tests for herpes infections allow for screening to reduce the risk of neonatal herpes.Objectives: To assess the potential effectiveness, cost effectiveness, and benefit of suppressive therapy among herpes simplex virus serodiscordant sex partners during pregnancy.Methods: Decision and economic analyses are used to compare the incidence and costs of neonatal herpes in California (2000) for three interventions: (1) no management; (2) current guidelines (caesarean delivery for women with lesions); (3) screening for women at risk and use of suppressive treatment in sex partners.Results: Screening and suppressive therapy are the most effective interventions, while current guidelines have limited effectiveness, but the latter provide the most cost effective results.Conclusions: While current guidelines are cost saving, they forgo a potential 82% decrease in neonatal herpes incidence that would be possible with screening and suppressive therapy if society were willing to pay the necessary US$363 000 per case prevented. To evaluate HSV screening and drug therapy completely, clinical trials and an economic assessment of infant mortality "value" to society are required. [ABSTRACT FROM AUTHOR]