We obtained a cDNA clone representing a partial RNA sequence of a human hepatitis C virus (HCV) isolate from Southern California. RNA was extracted from the liver tissue of a patient with post-transfusion hepatitis, and used for cDNA synthesis and polymerase chain reaction (PCR) amplification using oligonucleotide primers specific for the prototype HCV RNA. The cDNA clone obtained contains 585 base pairs of HCV sequences and represents the region encoding the putative nonstructural protein NS3 of HCV. Sequence analysis of this clone showed that it shares 93.8%, 78.7% and 79.6% similarity, respectively, with the previously published American, Japanese and Taiwanese isolates at the nucleotide level, indicating the heterogeneity of HCV RNA in different geographic areas. By contrast, it shares 97.3%, 92.9% and 92.9% with these respective isolates at the amino acid level, suggesting the functional conservation of viral genes.