This study was undertaken to examine the natural history of parvovirus B19 infection in persons without a known immune defect in terms of both clinical symptoms and immune responsiveness to the virus. Fifty-three patients with acute B19 infection (positive for serum anti-B19 IgM) were studied; symptoms at acute infection were rash and arthralgia (n = 26), rash (n = 7), arthralgia (n = 16), aplastic crisis (n = 3), and intrauterine fetal death (n = 1). Patients were followed for 26-85 months (mean 57 months) and reassessed for persistent symptoms, anti-B19 antibodies, and antibodies to the unique region of B19 VP1. There were 23 cases of arthralgia persisting for longer than 1 year after acute infection. One of these patients, a 48-year-old woman at follow-up, had had persistent arthralgia for 4 years following acute B19 infection, had rheumatoid factor at a titre of 1920 IU/ml detected at follow-up, and had been independently diagnosed as having rheumatoid arthritis at the time of follow-up. All 53 patients were positive for serum anti-B19 IgG compared to 45 of 53 age- and sex-matched control patients, a significant difference (two-tailed P value = 0.008). All test patients at follow-up and control patients were negative for serum anti-B19 IgM and antibodies to the unique region of B19 VP1. Serum from acute infection from 33 of 53 test patients was tested for antibodies to the unique region of VP1, and 16 of these were positive. The presence of this antibody did not correlate with subsequent duration of symptoms but did correlate with a short interval between symptom onset and blood sampling. The unique region of B19 VP1 is known to be crucial for a successful humoral response to the virus, and it seems that the antigenic role played by this region is important only during the acute phase of B19 infection.