We evaluated the risk of hepatitis C virus transmission through household contact with chronic carriers using nucleotide sequence analysis. Chronic hepatitis C patients (76 patients) were divided into two groups: familial transmission of hepatitis C virus was studied in group A (53 patients); group B (23 patients) served as nonfamilial controls for group A. Of 88 family members of group A patients, 18 (20%) had elevated serum ALT levels, 20 (23%) had antibodies against hepatitis C virus and 16 (18%) had hepatitis C virus RNA in serum. Nucleotide sequences of the region of the hepatitis C virus genome spanning the core and envelope genes were compared among the three groups. In group B, the average nucleotide sequence homology was 91.0% +/- 2.29% (a pairwise comparison was made for each of the patients; n = 253). Isolates from two family members were significantly more homologous to isolates from corresponding patients in group A than to isolates from group B patients. Of the two isolates from family members, one was from a child whose mother was a patient (97.7% homology) and one was from a spouse (98.1% homology). These results strongly suggest familial transmission of the same hepatitis C virus strain. Further studies are necessary to elucidate the route of intrafamilial transmission.