We describe a case of symptomatic acute infection with HCV in a woman whose sexual partner had chronic hepatitis C. The patient cleared HCV RNA 8 weeks after the onset of acute hepatitis and was found to be persistently HCV-RNA negative during 90 weeks of follow-up. Part of the E-2 region of HCV was directly sequenced in the patient and her sexual partner. Four local controls with subtype-1a infection and 9 1a isolates obtained from GenBank were analyzed. The average nucleotide divergence between the sequences of the infected patient and her sexual partner was 5.1%, compared with an average nucleotide divergence of 19.4% (range 16.6-21.8%) between the sequences of the patient and those of controls. Comparison of the phylogenetic trees in the partial E-2 region showed that the sequence of the patient was closely related to that of her sexual partner. Our findings suggest that the infection was transmitted to the patient from her sexual partner. The resolution of acute hepatitis C in this case was probably related to the host rather than to intrinsic characteristics of the HCV genome.