To determine the relationship between the expression of epidermal growth factor receptor (EGFR) and the presence or type of human papillomavirus (HPV) in cervical squamous intraepithelial lesions (SIL), paired colposcopically directed cervical biopsies were obtained from 88 patients referred for abnormal Papanicolaou smears. One biopsy was formalin-fixed and processed for conventional light microscopy, and the other was immediately frozen. A portion of the frozen tissue was used for Southern blot HPV DNA hybridization and a portion for immunohistochemical studies for EGFR using a monoclonal antibody. Forty-seven cases were SIL and 41 were normal. In 41 (87%) of the cases of SIL and in eight (20%) of the normal cases, HPV DNA was detected. Of the SIL cases, HPV 16 was the most frequently detected type, being present in 12 (25%), followed by 10 (21%) types 31 or 35, nine (19%) types 52 or 56, five (11%) uncharacterized types, three (6%) type 18, and two (4%) multiple types. Regardless of histology, EGFR was detected in all cases. In normal cases, EGFR expression was detected in the basal cells only and in SIL in abnormal proliferating parabasal cells such that it correlated with the grade of SIL. When stratified by grade of SIL, no differential expression of EGFR was seen in cases where HPV was detected; in contrast, in cases where no HPV was detected, no differential expression was seen between cases of different HPV type. Thus, EGFR is expressed by all proliferating squamous epithelial cells and as such correlates with the grade of SIL.(ABSTRACT TRUNCATED AT 250 WORDS)