Hepatitis C virus quasispecies in six patients from three families were separated by single strand conformation polymorphism analysis and by determination of nucleotide sequences of envelope regions containing the E1 gene segment and hypervariable region-1 of each quasispecies. Four of the six patients had multiple quasispecies. Phylogenetic analyses indicated that all quasispecies from one individual were highly homologous to each other. The homology was higher in the E1 gene segment than in hypervariable region-1. Furthermore, all quasispecies found in members of one family (husband and wife) were also highly homologous, suggesting direct intrafamilial transmission. The direction of hepatitis C virus variation in hypervariable region-1, however, seems to differ depending on the host in intrafamilial transmission.