In the 2000/01 season, the size of the influenza epidemic in the Netherlands was exceptionally small. Since the start of the Continuous Morbidity Registration of the Netherlands Institute of Primary Health Care (NIVEL) in 1970, the peak incidence of influenza-like illnesses has never been so low. The aetiology of the epidemic was also unusual. Most remarkable was the relatively extensive circulation of subtype H1N1 and the low activity of subtype H3N2. The epidemic started in week 1 of 2001 and ended in week 8. The antigenic properties of the influenza A (H1N1) viruses closely resembled those of the vaccine strain A/New Caledonia/20/99. This new variant of subtype H1N1 was first isolated in Asia in 1995 and was only (sporadically) detected in the Netherlands in the 1999/2000 season. Phylogenetic analysis showed that these viruses represent a new line of subtype H1N1. Following the influenza-activity caused by H1N1 viruses in the 2000/01 season, a small number of B and H3N2 viruses were also isolated up to week 19. Antigenically, these viruses were identical to those obtained in the previous years. On the basis of the antigenetic analyses presented, it can be concluded that the vaccine provided good protection against the circulating influenza viruses in the 2000/01 season. The World Health Organization recommends that influenza vaccines intended for use in the 2001/02 season of the northern hemisphere should contain the following, or antigenically similar, strains: A/Moscow/10/99 (H3N2), A/New Caledonia/20/99 (H1N1), and B/Sichuan/379/99.