Background: Needlestick accidents are a problem among health care workers. Using sensitive new assays, we evaluated the prevalence and features of hepatitis C virus (HCV) infection following a needlestick accident. Method: The clinical outcome and evolution of serum HCV markers were assessed in 90 hospital employees (recipients) who sustained needlestick injuries (selected from 146 episodes) involving 92 patients with clinical non-A, non-B hepatitis (donors). Results: Of the 92 patient donors, 62 (67%) and 88 (96%) were anti—C100-e and second-generation anti-HCV positive, respectively, at the time of the needlestick accident. During the follow-up period (≥ 6 months), acute non-A, non-B hepatitis developed in three of 90 recipients about 1 month after the accident. The three respective donors were positive for serum HCV-RNA at the time of the accident. Two of the three recipients became HCV-RNA positive just after the onset of hepatitis, and subsequently, HCV antibodies developed. None of the remaining 87 recipients had any clinical or laboratory evidence of hepatitis during follow-up, or experienced seroconversion for anti— C100-3 or second-generation anti-HCV. We measured additional HCV markers in 20 of the 89 donors; 16 had evidence of HCV infection (HCV-RNA). However, none of the respective recipients of any of these 20 became positive for HCV markers during follow-up. Conclusion: Although transmission of HCV infection by needlestick injury may be infrequent, such transmission does occur. Appropriate precautions should be taken to protect health care workers. (Arch Intern Med. 1993;153:1565-1572)