In a cross-sectional study we have investigated serological and T-helper (Th) cell responses to human papillomavirus type 16 (HPV-16) L1 in women with HPV-16 related diseases and related them to cervical histology and HPV DNA status. Using a virus-like particle (VLP) based ELISA to detect antibodies to the HPV-16 L1 capsid protein, 45% (33/73) of women with cervical dysplasia, 40% (2/5) of women with cervical cancer, 36% (4/11) of healthy adult female controls and 6% (2/35) of healthy children were found to be seropositive. Amongst women with cervical dysplasia, the highest levels of seropositivity were found in those who were HPV-16 DNA positive (60%, 15/25) or positive for any of the "high-risk' HPV types, 16/18/33 (58%, 18/31), when compared with those with HPV type "X' (25%, 5/20) or with healthy children (6%, 2/35; P < 0.05 for all comparisons). There was a trend for women with cervical dysplasia to show an increased level of seropositivity with increasing grade of lesion. There was no direct correlation found between seropositivity and Th cell responses in all groups studied. However, a combined analysis of each individual's Th and B cell responses suggests that a Th1 pattern of response is predominant amongst healthy adult controls (80% of responders) but reduced in women with cervical dysplasia (55% of responders). A trend towards a decrease in Th1 type responses was also noted with increasing grade of dysplastic lesion. These findings provide further evidence for the importance of the Th response in the control of genital HPV infections.