Human parechoviruses (HPeVs) mainly infect young children, causing mild gastrointestinal and respiratory diseases; however, HPeV type 3 (HPeV3) causes severe systemic diseases in young infants. To clarify the characteristics of HPeV infections from the aspects of seropositivity and epidemiology, we measured neutralizing antibody titres against HPeVs in individuals of in different age groups and isolated HPeVs from various clinical specimens in Niigata, Japan. The seropositivity to HPeV1, 3, and 6 was higher in older age group. HPeV1 and HPeV6 seropositivities were maintained in adults, whereas HPeV3 seropositivity was significantly lower in subjects aged >40 years (P < 0·001, P = 0·003). This result suggests that adults have increased susceptibility to HPeV3 as they lack neutralizing antibodies against HPeV3. Of the HPeV isolates, HPeV1 and HPeV6 frequently caused gastrointestinal symptoms. Moreover, gastroenteritis patients with HPeV1 and HPeV6 were mainly aged 6 months–1 year and ⩾2 years, respectively. In contrast, only HPeV3 was isolated from neonates and young infants with sepsis or sepsis-like syndrome, often with respiratory symptoms. These results suggest that clinical symptoms are clinically related to HPeV genotype and patients’ age.