The development over time of antibodies to human papillomavirus type 6 (HPV 6) was studied prospectively in a group of 26 condyloma patients receiving multiple treatments, as well as in 17 healthy subjects with a new HPV 6 infection. The condyloma patients provided serum samples during 2-12 visits over a period of 1-20 months, and the levels of IgA, IgG and IgM antibodies to HPV 6, 11 and 16 capsids, and to HPV 6-derived peptide antigens were determined. Among the capsid antibodies, the IgG and IgA responses against HPV 6 were the most prominent, whereas IgM was detected only in a few patients. During follow-up, seroconversion to HPV capsids was found in six patients and antibody peaks disappeared during follow-up in nine patients. There was no association between serology and cure of the wart. One hundred twenty subjects who reported multiple sexual partners, but found negative for HPV DNA at multiple anogenital and oral sites, provided serum samples and swabs for HPV DNA analysis at 2-7 visits during 4-74 months. Seventeen subjects acquired HPV 6 DNA and were included in the study. Serum IgA, IgG and IgM antibodies to HPV 6 capsids were induced concomitantly with the acquisition of viral DNA (P = 0.02, 0.002 and 0.006, respectively), and declined again when the viral DNA was no longer detectable. In conclusion, antibodies to HPV 6 did not predict the clinical course of condylomatous disease, but appear to be useful mainly as epidemiological markers of viral exposure.