To assess the utility of a new, rapid, economical procedure that may prove valuable in cervical screening, Fourier transform infrared (ir) spectroscopy was performed on 25 cervicovaginal lavage specimens from women referred for colposcopy on the basis of a cytological abnormality detected on their Pap smear and whose lavage specimen was positive for human papillomavirus. Of the 18 classed as CIN I or less by histopathology, 11 showed band frequencies that deviated only slightly from spectra that characterize normal cervical cells and 3 of 5 “atypia” specimens had spectra identical to normal. Two of 3 classed as CIN II had spectra only slightly more abnormal to these 11. In the case of 2 graded as CIN I, several bands were similarly altered in the direction of the pattern seen for 4 CIN III specimens. A further CIN I sample gave a spectrum that was even further shifted toward the latter and the remaining CIN I sample had a pattern that matched the 4 CIN IIIs. The most obvious change in each of the CIN IIIs was an additional peak at 972 cm-1 and this has been suggested as a key indicator for malignancy. One of the 3 CIN IIs had this peak. Other characteristic spectral changes were seen as well in the CIN III samples. High-risk HPV18 was present in 3 of the CIN III samples, as well as in one specimen classed as atypia, but having an abnormal ir spectrum. Low-risk HPV 6 or 11 was seen along in samples with a normal or slightly abnormal ir spectrum, but never in those that showed an ir pattern that was abnormal. The current study has therefore shown complete concordance between ir spectral findings and histopathology result in the case of CIN III specimens, but less precise matching for other grades of CIN. The spectral differences revealed by ir spectroscopy are likely to characterize molecular abnormalities in cervical cells during progression to cancer and may therefore have potential in assisting with clinical decision making. More studies will, however, be required to establish the place of this technique in cervical screening.