AIMS--To study the value of non-isotopic in situ hybridisation (NISH) in detecting human papillomavirus (HPV) infection in female genital lesions positive for the virus by conventional histology but negative by filter DNA hybridisation. METHODS--Forty three cases, which showed the histological hallmarks of the HPV infection but produced negative results in filter dot blot hybridisation tests (Vira Pap and Vira Type kits), were identified in the course of an investigation of 304 vaginal, vulvar, and cervical samples from 267 patients. These cases were studied by NISH for the presence of HPV infection. RESULTS--In 28 (65%) of the cases NISH gave a positive hybridisation signal. In 26 cases (96%) the signal was diffuse, and in two (4%) punctate or diffuse, representing episomal and episomal or integrated HPV DNA, respectively. In most cases only a few HPV positive cells were discernible. CONCLUSION--NISH is a more sensitive technique than dot blot hybridisation, detecting HPV infection in most cases which show histological HPV atypia but which remain negative in filter DNA hybridisation. Thus NISH is useful as an additional technique to verify the presence of HPV in lesions which remain negative in filter hybridisation tests.