To clarify the hypothetical etiologic role of human papillomavirus (HPV) for micropapillomatosis labialis, the frequency of HPV infection was compared by dot blot hybridization techniques between vulvar samples from 34 women with micropapillomatosis labialis and 34 women with normal vulvar skin. Although more patients with micropapillomatosis labialis than controls had HPV DNA detected, this was not statistically significant (eight of 34 versus three of 34, respectively; and two of 23 versus one of 34, respectively, when only biopsies were analyzed). In a second part of the study, 22 patients with micropapillomatosis labialis were followed without treatment; the lesion regressed in 45% and persisted in 55% of the patients. Among 11 patients treated with CO2 laser, 5-fluorouracil, or trichloroacetic acid, the lesion persisted in three cases. These results suggest that these introital changes are unrelated to HPV and that a high percentage will regress without treatment.