A study of 37 women with typical condylomas and so-called squamous micropapilloma was undertaken to determine their response to systemic interferon and/or podophyllin treatment. Thirty lesions were classified as condylomas and 9 as squamous micropapillomas; two women had both lesions. Twenty-six (87%) of 30 condylomas responded, whereas only 1 (11%) of the 9 cases of micropapillomatosis showed a partial response (P less than .001) to podophyllin and/or interferon. Twenty-six biopsies from condylomas in which sufficient DNA was available for analysis contained human papillomavirus (HPV) DNA sequences that hybridized to an HPV 6 + 16 probe mix under nonstringent conditions. In contrast, HPV DNA sequences could not be detected in any of the nine cases of micropapillomatosis. Immunoperoxidase studies performed on these lesions failed to demonstrate viral capsid antigen. Thus, despite certain similarities in the clinical presentation and microscopic features of condylomas and squamous micropapillomas, it is not clear at present whether micropapillomas are HPV-related lesions.