Congenital parvovirus infection was diagnosed in two liveborn premature infants born at 24 and 35 weeks of gestational age. The illnesses were associated with placentomegaly, petechial rash, edema, hepatomegaly, anemia and thrombocytopenia, respiratory insufficiency, and death at 5 and 6 days of age. The syndromes exhibited by these cases shared common but nonspecific features with other life-threatening congenital infections. Serological studies in one case supported the diagnosis of parvoviral infection. Postmortem examination of both revealed nuclear inclusions in erythroid precursor cells characteristic of parvovirus infection. Use of the polymerase chain reaction confirmed the presence of parvovirus DNA in one of the cases. Intrauterine parvovirus B19 infection is most commonly associated with hydrops fetalis, "transient" hydrops, or a favorable outcome in infants found to be viremic after birth. These and previously reported examples of congenital B19 disease exemplify an exceptional form of human parvovirus infection.