The gene expression of human papillomavirus (HPV) 33, which can be detected both in benign and malignant genital tumors, was analyzed in a cervical condyloma acuminatum by in situ hybridization using open reading frame-specific RNA probes. Viral mRNA concentrations increased with the degree of differentiation of the keratinocytes. The probes for reading frames E4 and E5 generated the most intense signals. The patterns of the specific viral mRNAs were very similar to those in condylomas induced by HPV 6 or 11, which are only rarely associated with malignancies. This implies that in tumors of the same degree of morphological differentiation the gene expression program of different HPV types is essentially identical. The pattern observed here most likely corresponds to a productive phase of viral infection.